Secret Relationship of Regulatory T cells, Tregs, on Basophils

MedicalResearch.com Interview with:
“Basophil” by GreenFlames09 is licensed under CC BY 2.0Jagadeesh BAYRY, DVM, PhD, HDR

Scientist CRCN/Associate Professor-INSERM
Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1138
Centre de Recherche des Cordeliers
PARIS , FRANCE

 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Basophils are rare granulocytes that are important for the protection against helminth parasites. In addition, basophils mediate T helper 2 responses, support B cell differentiation, and thus establish a vital link between innate and adaptive immunity. Although rare in number, basophils are implicated in various pathological conditions due to the fact that they undergo rapid activation in response to a wide range of stimuli they receive. These stimuli induce the release of diverse immune mediators including cytokines and mediators of hypersensitivity reactions histamine and leukotriene. Basophils are well known for their pathogenic role in allergic diseases. Recent data also advocate basophils in the pathogenesis of autoimmune and other inflammatory diseases. Therefore, considering the impact of dysregulated functions of basophils on the immune response in various diseases, we deliberated that it is essential to understand the regulatory mechanisms by which basophils are kept in check.

Among immunoregulatory cells, CD4+CD25+FoxP3+ regulatory T cells (Tregs) have been widely studied for their role in immune tolerance and in the maintenance of immune homeostasis. Tregs modulate autoimmune and inflammatory responses by exerting direct suppressive effects on various immune cells including dendritic cells, T cells, macrophages, monocytes, B cells, neutrophils, natural killer cells, and mast cells. In view of emerging reports on the role of basophils in various pathological conditions, we investigated if Tregs are able to control the activation and functions of basophils.

In contrast to the central dogma on Tregs as immunosuppressors, we discovered that human basophils are refractory to Treg-mediated suppression. On the contrary, we found that Tregs stimulate resting basophils to induce the expression of activation markers CD69, CD203c, and CD13, and release cytokines IL-4, IL-8, and IL-13. Treg-induced activation of basophils involves IL-3 and STAT5 but was not contact-dependent. These results provide evidence of direct positive effects that human Tregs have on basophil activation and reveal a previously unrecognized feature of this cell subset well known for immunosuppressive functions.  Continue reading

Specific Types of Inflammation Tied to Cardiovascular Disease

MedicalResearch.com Interview with:

Dr. Karl T. Kelsey, MD, MOH Professor of Epidemiology and Pathology and Laboratory Medicine Fellow, Collegium Ramazzini Providence, R.I. 02912

Dr. Kelsey

Dr. Karl T. Kelsey, MD, MOH
Professor of Epidemiology and Pathology and Laboratory Medicine
Fellow, Collegium Ramazzini
Providence, R.I. 02912

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: ​There is a large literature suggesting that the ratio of neutrophils to lymphocytes (the neutrophil to lymphocyte ratio or NLR) in the peripheral blood at the time of diagnosis is robustly predictive ​of outcome in acute cardiovascular disease.

We were curious to know if the peripheral blood profile and this ratio was a feature of the disease process, since, to our knowledge, this had not been investigated in a prospective study.  Hence, we used the resources of 2 prospective studies to assess this question, the Jackson Heart Study and the Normative Aging Study.  In both cases, the NLR predicted all cause mortality and, in the Jackson Heart Study, where we had well adjudicated outcomes, the NLR predicted various specific cardiovascular outcomes as well. Interestingly, the outcome was also modified by a well known genetic polymorphism of African origin that results in a relative neutropenia.

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Inflammatory Cells That Suppress Skin Allergic Reactions Identified

MedicalResearch.com Interview with:
elstarNidhi Malhotra PhD

Boston Children’s Hospital
Division of Allergy and Immunology
Senior Scientist at Elstar Therapeutics Inc.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Allergies such as Atopic Dermatitis (AD) are rampant in the industrialized nations. Why are we more predisposed to developing hypersensitive reactions to innocuous proteins (allergens) is not well understood. To gain better understanding and to develop better therapies, we need to first delve deeper into how our immune system regulates homeostasis in tissues such as skin. The main cell types that thwart inflammatory reactions are known as regulatory T cells. These cells are generated in thymus and reside in secondary lymphoid tissues but they are also prominent at tissue sites such as in dermal layer of skin. In this study, I focused on understanding how Tregs resident in skin are distinct from the Tregs in secondary lymphoid organs such as lymph nodes (LNs). I uncovered that functioning of Tregs in skin is underpinned by a distinct set of genes. One main gene that I found to be highly expressed in skin Tregs but not in LN Tregs is Rora, which encodes for the transcription factor ROR alpha (RORa).

This observation was intriguing as previous studies had elucidated the requirement of RORa in the development of inflammatory type-2 innate lymphoid cells (ILC2s) and it has been considered the antagonizing RORa functioning would curb allergic responses. However, I observed that Tregs require RORa to suppress allergic responses. In particular, RORa regulates the expression of a TNF receptor family member DR3, which binds to the cytokine TL1A. TL1A has a role in enhancing suppressive activity of Tregs while also enhancing type-2 cytokine production from ILC2s. Hence, in the absence of DR3 in Tregs, we believe more TL1A is available to ILC2s resulting in unrestrained allergic responses.  Continue reading

Toxin-Producing Bacteria Staph Aureus Induces Skin Inflammation

MedicalResearch.com Interview with:

Lloyd S. Miller, M.D., Ph.D. Vice Chair for Research, Department of Dermatology Associate Professor of Dermatology, Infectious Diseases, Orthopaedic Surgery & Materials Science and Engineering Faculty Member, Cellular and Molecular Medicine (CMM) and Pathobiology Graduate Programs Johns Hopkins Department of Dermatology Baltimore, MD 21231

Dr. Miller

Lloyd S. Miller, M.D., Ph.D.
Vice Chair for Research, Department of Dermatology
Associate Professor of Dermatology, Infectious Diseases, Orthopaedic Surgery & Materials Science and Engineering
Faculty Member, Cellular and Molecular Medicine (CMM) and Pathobiology Graduate Programs
Johns Hopkins Department of Dermatology
Baltimore, MD 21231 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Staphylococcus aureus is a common bacterial skin pathogen and its abundance is greatly increased on affected skin of eczema patients, especially during disease flares. However, how S. aureus induces skin inflammation and exacerbates the skin inflammation is incompletely understood.

In this study, we found that S. aureus exposure of mouse skin induced skin inflammation through an inflammatory mediator known as IL-36.

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Chronic Inflammation in Midlife May Predispose To Smaller Brain Volumes and Memory Ability In Seniors

MedicalResearch.com Interview with:
Keenan A. Walker, PhD
Johns Hopkins University School of Medicine
Baltimore, MD

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is quite a bit of evidence linking immune function with dementia. For example, several of the risk genes for Alzheimer’s disease are known to play a key role in immune functioning and the regulation of inflammation. We conducted the current study to determine whether systemic inflammation earlier in life might be a risk factor for neurodegeneration decades later. This long temporal window allows us to get closer to understanding causality. That is, which comes first – systemic inflammation or brain volume loss.

Using a large community sample, we found that individuals with higher levels of blood inflammatory markers during midlife tended to have smaller brain volumes in select regions and reduced memory ability as older adults. We found the strongest associations between systemic inflammation and brain volume loss in brain regions most vulnerable Alzheimer’s disease.

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Beta-Blockers Reduce Heart Attack Size By Limiting Inflammation

MedicalResearch.com Interview with:

Borja Ibáñez MD Spanish National Centre for Cardiovascular Research Madrid

Dr. Ibáñez

Borja Ibáñez MD
Spanish National Centre for Cardiovascular Research
Madrid

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Acute myocardial infarction (heart attack) is a severe condition responsible for thousands of deaths every year and with important long-term consequences for survivors. Best treatment for acute myocardial infarction is a rapid coronary reperfusion.

Upon reperfusion, all inflammatory cells and mediators accumulated in the circulation during the infarction process, enter into the myocardium and causes an extra damage to the heart. Activated neutrophils play a critical role in this damage occurring upon reperfusion. The final size of infarction is the main determinant for mortality and long-term morbidity. The possibility of limiting the extent of infarcted tissue is of paramount importance.

Betablockers have been used in patients for more than 4 decades, mainly to treat arrhythmias and high blood pressure. Recently the same group of investigators demonstrated that the very early administration (i.e. during ambulance transfer to the hospital) of the betablocker “metoprolol” was able to reduce the size of infarction in patients. The mechanism by which metoprolol was protective in patients suffering a myocardial infarction was unknown.

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Protective Bacteria May Reverse Inflammation In Some Forms of IBD

MedicalResearch.com Interview with:
Justin E. Wilson, Ph.D 
On behalf of the authors
Research Assistant Professor – Laboratory of Jenny Ting
Department of Genetics
Lineberger Comprehensive Cancer Center
The University of North Carolina at Chapel Hill
Chapel Hill, NC 27599

MedicalResearch.com: Could you provide me with some background on this project? Why did you decide to do this research project? What prior work led up to this latest paper?

Response: Previous work from our lab and others discovered two major points about NLRP12:
a) NLRP12 suppresses inflammation in response to bacterial components
b) NLRP12 provides protection against the inflammatory bowel disease colitis and colitis-associated colon cancer (i.e., Nlrp12-defcient mice have greater colon inflammation and inflammation-driven colon cancer).
Therefore, we wanted to know if Nlrp12 was regulating inflammation in the colon by responding to the trillions of intestinal microbes collective referred to as the microbiome. Mounting evidence also indicates that the immune system both responds to and influences the composition of the intestinal microbiome during intestinal health and disease, and we hypothesized that NLRP12 could be one of the important immune components during this process. Moreover, we were also interested in this topic because targeting the microbiome to treat inflammatory disorders and other diseases is an attractive method that has many advantages over immune suppression.

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Anti–HIV Drug Candidate Prevents Intestinal Inflammation

MedicalResearch.com Interview with:
Prof. Jamal Tazi

Director, Institute for Molecular Genetics
CNRS and University of Montpellier and Executive Committee Member
ABIVAX

MedicalResearch.com: What is the background for this study?

Response: Its long been established that people with HIV, even those treated successfully with antiretroviral treatment, exhibit significantly higher levels of chronic inflammation than HIV-negative people. The causes of this inflammation are many – ongoing viral replication, often in the so-called viral reservoirs, leaky gut syndrome, concomitant viral infections (eg CMV, hepatitis etc).

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Parkinson’s Disease Linked To Increase in Number of Inflammatory Markers

MedicalResearch.com Interview with:

Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland

Dr. Yong Cheng

Yong Cheng, PhD, post-doc fellow
Section on Cellular Neurobiology
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland

MedicalResearch.com: What is the background for this study?

Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with  Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls.

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Inflammatory Molecule Links Metabolic Environment and Innate Immunity

MedicalResearch.com Interview with:

David Underhill, PhD Professor of Biomedical Sciences Research scientist, F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute Cedars-Sinai

Dr. David Underhill

David Underhill, PhD
Professor of Biomedical Sciences
Research scientist, F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute
Cedars-Sinai
Los Angeles, CA

MedicalResearch.com: What is the background for this study?

Response: “Innate immunity” is the body’s natural resistance to microbial infection and stands in contrast to “adaptive immunity,” which is the body’s learned response to infection (e.g. antibodies and vaccines). In the standard model of innate immunity that has emerged over the last several decades, scientists have come to understand that the human genome encodes many “receptors” that have evolved as sensors for specific common microbial molecules, such as bacterial or viral DNA or components of bacterial or fungal cell walls. The job of these receptors is to survey the environment (skin, blood, etc.) for potentially dangerous microbes and initiate inflammatory responses if they are found. These activities are essential for defense against infection, and people and animals with defects in these sensors or the responses they trigger can be susceptible to infection.

My laboratory has been interested for more than a decade in identifying these innate sensors and the microbial targets that they recognize. In this study, we were looking for the sensor that allows white blood cells (e.g. macrophages and dendritic cells) to detect Gram-positive bacterial cell walls and trigger a specific inflammatory response: secretion of the potent inflammatory mediator interleukin-1β (IL-1β).
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Inflammatory Biomarkers May Presage Development of Alzheimer’s

MedicalResearch.com Interview with:

Inflammatory Biomarkers May Presage Development of Alzheimer's

Prof. Paul Morgan

Professor B. Paul Morgan
Director, Systems Immunity Research Institute
Institute of Infection and Immunity
School of Medicine
Cardiff University

MedicalResearch.com: What is the background for this study?

Response: Inflammation is a normal response of the body to infection or injury; however, it is well known that inflammation also has a dark side and when it escapes normal controls can cause disease. Some illnesses, like rheumatoid arthritis, have been known for many years to be caused by rogue inflammation and most of the drugs used to treat work by suppressing the inflammation (anti-inflammatories). More recently, it has become clear that inflammation is behind many other diseases that were previously thought of as diseases of ageing caused by wear and tear and lifestyle – these include heart disease and some brain diseases, notably Alzheimer’s disease the commonest cause of dementia. Evidence that inflammation is one of the drivers of disease has come from many sources, including some where it was noticed that people on long-term anti-inflammatory drugs for other reasons appeared to be protected from developing Alzheimer’s disease.

A problem is that Alzheimer’s disease, despite the name, is not a single disease but rather a group of conditions with similar symptoms, and inflammation is likely to be a cause in only some of the patients; further, most of the inflammation might be occurring very early in the disease, even before symptoms are obvious. So, there is an urgent need for a simple test or set of tests that can be used in individuals with the very earliest hints of Alzheimer’s disease – mild memory loss – that will pick out those who have brain inflammation and are most likely to develop Alzheimer’s disease. It might then be possible to treat this select group with anti-inflammatory drugs that will reduce brain inflammation and slow or stop progression of the disease.

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Genetic Links To Fatal Inflammatory Flu Reaction Discovered

Grant S Schubert MD, PhD Clinical Fellow, Division of Rheumatology Cincinnati Childrens Hospital

Dr. Schulert

MedicalResearch.com Interview
Grant S Schulert MD, PhD
Clinical Fellow, Division of Rheumatology
Cincinnati Childrens Hospital 

Medical Research: What is the background for this study? What are the main findings?

Dr. Schulert: Influenza infection causes millions of illnesses annually, but most of those are relatively mild.  In a subset of cases, patients can become critically ill, even if they are relatively young and healthy.  Several previous reports had observed in these critically ill patients features of a hyperinflammatory syndrome known as HLH (hemophagocytic lymphohistiocytosis) or MAS (macrophage activation syndrome).  This hyperinflammation can be triggered by other infections as well as in a subtype of juvenile arthritis, but there is also a familial form occurring in early childhood with known genetic causes.  Our questions with this study were

1) how often are features consistent with HLH/MAS seen in fatal H1N1 influenza infections and
2) do patients with fatal H1N1 infection have genetic mutations associated with HLH/MAS?

Our collaborator Paul Harms, MD, and his team at the Michigan Center for Translational Pathology, University of Michigan Medical School identified 16 cases of fatal H1N1 influenza infection.  Based on their clinical features, between 41-88% of these patients could be categorized as having a hyperinflammatory HLH/MAS.  We then used processed tissue samples from the patients for whole exome genetic sequencing, which reads the entire genetic code of every gene in a person. Five patients carried mutations in genes which cause HLH, and several others carried mutations in genes linked to MAS.  This suggests that there may be genetic risk factors for developing fatal hyperinflammatory syndromes in H1N1 infection.

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No Evidence of Anti-Inflammatory Mediator Increase From Fish Oil Ingestion

Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of PennsylvaniaMedicalResearch.com Interview with:
Carsten C. Skarke MD
Research Assistant Professor of Medicine
McNeil Fellow in Translational Medicine
Institute for Translational Medicine and Therapeutics
Perelman School of Medicine
University of Pennsylvania

Medical Research: What is the background for this study? What are the main findings?

Dr. Skarke: A growing body of publications suggests anti-inflammatory actions of fish oils. These health benefits are proposed to emerge from lipids called specialized pro-resolving mediators, (SPMs), which can be formed from omega-3 polyunsaturated fatty acids found in fish. A limitation to date, though, in this field is that there is little evidence of their formation in humans. And the cases where presence of these lipids is reported in humans, less rigorous analytical approaches, such as enzyme immunoassay (EIA), radioimmunoassay (RIA) or mass spectrometry without internal authentic standards, have been used. Thus, the specific aim for our study was to use state-of-the-art mass spectrometry to identify and quantify these specialized pro-resolving mediators.

Several aspects of our study design set us apart from what was done in previous studies.

  • First, we biased our ability to detect SPMs formed in healthy volunteers by giving fish oil in high doses which had been previously shown to influence blood pressure and platelet aggregation under placebo-controlled conditions.
  • Second, we also looked at lower doses of fish oil, those more commonly consumed by the general public, for the formation of SPMs during an acute inflammatory response and its resolution.
  • Third, we relied in our measurements of SPMs on authentic internal standards. These deuterated lipids, d4-resolvin E1 for example, facilitate distinct identification of the naturally formed lipid.
  • And fourth, we achieved very low limit of detection levels, below 10 pg/ml for resolvin E1, for example.

The surprising finding of our studies is that we failed to detect a consistent signal of SPM formation in urine or plasma of healthy volunteers who had taken fish oil. Even more surprising was that we found no alteration in the formation of SPMs during the resolution of inflammation. These results let us question the relevance of endogenous specialized pro-resolving mediators to the putative anti-inflammatory effects of fish oils in humans.

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Study Examines Chronic Inflammation of Traumatic Brain Injury

Alan I Faden, M.D. David S. Brown Professor in Trauma Professor, Departments of Anesthesiology, Anatomy & Neurobiology, Neurosurgery, and Neurology Director, Center for Shock, Trauma & Anesthesiology Research (STAR) University of Maryland School of MedicineMedicalResearch.com Interview with:
Alan I Faden, M.D.
David S. Brown Professor in Trauma
Professor, Departments of Anesthesiology, Anatomy & Neurobiology, Neurosurgery, and Neurology
Director, Center for Shock, Trauma & Anesthesiology Research (STAR) University of Maryland School of Medicine

Medical Research: What is the background for this study? What are the main findings?

Dr. Faden: Accumulating clinical and pre-clinical research data indicate that traumatic brain injury (TBI) can lead to chronic progressive neurodegeneration. In this regard, most attention has focused on the connections between TBI and with Alzheimer disease (AD) or Chronic Traumatic Encephalopathy (CTE). However, recent epidemiological studies raise questions about the association between TBI and AD, and CTE is likely a less common end-stage result resulting from complex pathobiological changes. In contrast, both older and newer studies underscore that traumatic brain injury can cause chronic neuroinflammation that leads to chronic neurodegeneration. In contrast to AD and CTE, the latter condition appears to be potentially treatable, even long after injury. Our paper critically assesses the mechanisms and treatment of chronic post traumatic neurodegeneration.

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Link Between Inflammation and Breast Cancer Explored

Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City MéxicoMedicalResearch.com Interview with:
Dr. Jorge Morales-Montor
Departamento de Inmunología
Instituto de Investigaciones Biomédicas
Universidad Nacional Autónoma de México
México City México

MedicalResearch: What is the background for this study?

Dr. Morales-Montor: Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped in several protein families referred as tumour necrosis factors, interleukins, interferons and colony stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis and metastasis, all phenomena in which cytokines are prominent players. The data we have hitherto let us suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer related disorders.

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Cesarean Delivery May Increase Risk of Childhood Inflammatory Diseases

Professor of Pediatrics Hans Bisgaard, MD, DMSc Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen, Denmark.

Prof. Bisgaard

MedicalResearch.com Interview with:
Professor of Pediatrics Hans Bisgaard, MD, DMSc
Copenhagen Prospective Studies on Asthma in Childhood
Herlev and Gentofte Hospital,
University of Copenhagen, Denmark

Medical Research: What is the background for this study? What are the main findings?

Prof. Bisgaard: The purpose of this study was to look for a shared risk factor for immunological diseases which make its debut in childhood. During the recent decades a parallel increase in prevalence of immune diseases such as asthma, allergy, inflammatory bowel disease, and type 1 diabetes have been observed in westernized countries. The rate of cesarean delivery has increased in the same period and has previously been associated with the development of some of these diseases. This study takes advantage of the unique and valuable nationwide registry data in Denmark to establish a large population based cohort (2 million term children) with 35 years of follow up (in the period 1977-2012). We found cesarean delivery to be a common risk factor for a range of childhood immunological diseases: asthma, juvenile arthritis, inflammatory bowel diseases, connective tissue disorders, immune deficiencies and leukemia, but with no association to psoriasis, celiac disease, and diabetes type 1.

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High Quality Diet Reduces Systemic Inflammation

Joana Alves Dias, MPH Department of Clinical Sciences in Malmö, Lund University Malmö, Sweden MedicalResearch.com Interview with:
Joana Alves Dias, MPH
Department of Clinical Sciences in Malmö,
Lund University Malmö, Sweden

Medical Research: What is the background for this study? What are the main findings?

Response: The evidence that chronic inflammation may be in the genesis of diseases such as cardiovascular disease, type-II diabetes, and certain types of cancer is increasing. It is suggested that lifestyle factors such as diet, physical activity, smoking, and alcohol consumption could influence the inflammatory state. Instead of focusing on single nutrient effects, we used a hypothesis-driven approach to food pattern studies, and constructed a diet quality index based on the Swedish Nutrition Recommendations and Swedish Dietary guidelines (DQI-SNR). The DQI-SNR consisted of 6 components. Individuals were assigned 0 when not adhering to a recommendation and 1 when adhering, resulting in total scores ranging from 0 to 6. We classified individuals in low (0 or 1 points), medium (2 or 3) and high (4-6 points) diet quality. We explored the association between the index scores and low-grade inflammation.

Our study indicates that adherence to a high quality diet is associated with lower systemic inflammation, as measured by several soluble and cellular biomarkers of inflammation, in middle-aged individuals. In other words, adherence to the general nutrition recommendations could help prevent the development of diseases associated with chronic inflammation. The anti-inflammatory effects of Mediterranean-like diets have been studied extensively, but this study focused on the Swedish dietary habits and recommendations for the Swedish population, and reached similar conclusions. Continue reading

Inflammation May Explain Why Glycemic Control Alone May Not Prevent Diabetic Heart Disease

Carlos F. Sánchez-Ferrer, M.D., Ph.D. Professor of Pharmacology Universidad Autónoma de Madrid, Spain.MedicalResearch.com Interview with:
Carlos F. Sánchez-Ferrer, M.D., Ph.D.
Professor of Pharmacology
Universidad Autónoma de Madrid, Spain.

Medical Research: What are the main findings of the study?

Dr. Sánchez-Ferrer: We were studying the possible ways of interaction between high glucose levels, which are found in diabetes mellitus, with vascular damage,
which is the most common and devastating consequence of this disease.
An intriguing fact is that a very strict control of blood sugar in
diabetic patients is not sufficient to avoid the development of such
diabetes-induced cardiovascular diseases. We think our results can
explain why this is happening.

Using cultured smooth muscle cells from the main human artery (aorta)
in the presence of high concentrations of extracellular glucose, we
observed:
1. In the absence of inflammation, excess glucose in the culture fluid
didn’t enter the cells.
2. When extra glucose was forced into the cells, no harm was done in
the absence of inflammation.
3. When the inflammation-stimulating protein interleukin-1 (IL-1) was
introduced, more glucose entered the cells.
4. With IL-1, the glucose entering the cells was metabolized via
chemical pathways that spur escalating inflammation, overwhelming the
cells’ ability to counteract it.
5. In the presence of the anti-inflammatory drug anakinra, which blocks
the activity of IL-1, the deleterious changes didn’t occur.

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Systemic Inflammation Linked To Depression and Psychotic Disorders

Dr Golam Khandaker Clinical Lecturer, Department of Psychiatry University of Cambridge MedicalResearch.com Interview with
Dr Golam Khandaker
Clinical Lecturer, Department of Psychiatry
University of Cambridge


Medical Research: What are the main findings of the study?

Dr. Khandaker: The study shows low grade systemic inflammation may have a role in the pathogenesis of depression and psychotic disorders. Low grade systemic inflammation may also be a common cause for chronic physical and psychiatric illnesses.

The study shows that higher serum levels of the circulating inflammatory marker, interleukin 6 (IL-6), in childhood is associated with nearly two-fold increased risk of developing depression and psychotic disorder in young adulthood. This association persisted after taking into account effects of age, sex, social class, ethnicity, body mass index, maternal depression, and past psychological and behavioural problem in the participant.

We studied a sample of 4,500 individuals from the Avon Longitudinal Study of Parents and Children birth cohort, taking blood samples at age 9 and following up at age 18, to see if they had experienced episodes of depression or psychosis. We excluded children with an infection at the time of blood test at age 9 years.
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Chronic Inflammation Associated With Increased Risk of Diabetes and Heart Disease

MedicalResearch.com Interview with:
Dr Alex Dregan
Lecturer in Translational Epidemiology and Public Health,
Division of Primary Care and Public Health Research
King’s College London, London

Medical Research: What are the main findings of the study?

Dr. Dregan: Our study showed that chronic inflammation was associated with increased risk of developing cardiovascular disease, specifically type II diabetes and coronary heart disease. The risk of cardiovascular disease increased with the severity of inflammatory disorders. In addition, inflammation also increased the risk of multiple morbidity (two or more cardiovascular diseases).

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PTSD and Plasma Marker of Inflammation CRP

Dr. Dewleen Baker MD Veterans Affairs (VA) San Diego Healthcare System, San Diego, California MedicalResearch.com Interview with:
Dr. Dewleen Baker MD
Veterans Affairs (VA) San Diego Healthcare System, San Diego, California


MedicalResearch.com: What are the main findings of the study?

Dr. Baker: The main finding of this study is that a marker of peripheral inflammation, plasma CRP may be prospectively associated with PTSD symptom emergence, suggesting that inflammation may predispose to PTSD.
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Unhealthy Aging and Chronic Inflammation

MedicalResearch.com Interview with:
Tasnime Akbaraly  PhD
Institut National de la Santé et de la Recherche Médicale
Montpellier, France

MedicalResearch.com: What are the main findings of the study?

Dr. Akbaraly: The aim of this study was to examine the association between chronic inflammation and a range of aging phenotypes, assessed approximately 10 years later in a large British population of men and women  -The Whitehall II Study-. As inflammation characterises a wide range of pathological processes, we considered several aging phenotypes, including cardiovascular disease (fatal and non-fatal), non-cardiovascular mortality and successful aging which encompasses optimal functioning across different physical, mental, and cognitive domains

We found that chronic inflammation characterized by high levels of interleukin-6 (>2 pg/mL) twice over the 5-year exposure period nearly halved the odds of successful aging after 10–years of follow-up compared to maintaining low levels of interleukin-6 (<1pg/mL twice over the exposure period). Chronic inflammation was also associated with increased odds of future cardiovascular disease and non-cardiovascular mortality in a dose-response fashion. These associations were found to be independent of socio-economic factors, health behaviours (smoking, physical activity), and conditions such as obesity as well as the use of anti-inflammatory drugs and acute inflammation. Continue reading

Obesity: Inflammatory Markers May Detect Risk of Diabetes, Heart Disease

MedialResearch.com Interview with:
Dr Catherine M. Phillips
Health Research Board Centre for Diet and Health Research
Room 4.033, Department of Epidemiology and Public Health
Western Gateway Building, University College Cork, Cork, Ireland

MedialResearch.com: What are the main findings of the study?

Answer: Obesity is associated with increased risk of diabetes and heart disease leading to reduced life expectancy. However in recent years it has been recognized that not all obese individuals are at increased risk – these individuals have been described as being metabolically healthy obese (MHO) in that despite carrying excess weight they do not have the typical abnormal metabolic features associated with obesity such as hypertension, insulin resistance and alterations to their lipid profile.

It is not clear what factors determine whether an obese person becomes metabolically healthy or unhealthy. In this study conducted at the Dept. of Epidemiology and Public Health at University College Cork, Ireland, we examined levels of a range of inflammatory markers in 2047 middle-aged Irish adults to investigate to what extent differences between metabolically healthy and unhealthy obese and non-obese male and female adults are explained by inflammatory status. Participants, who were between the ages of 50 and 69, completed lifestyle questionnaires, physical and clinical assessments, and underwent blood testing so their body mass index (BMI), metabolic profiles and inflammatory markers could be determined. We found that, regardless of a person’s BMI, having a favorable inflammatory profile was associated with being metabolically healthy. Specifically metabolically healthy individuals presented with lower levels of complement component 3, C reactive protein, tumour necrosis factor alpha, interleukin 6, plasminogen activator inhibitor-1, reduced white blood cell count and higher adiponectin levels compared to their metabolically unhealthy counterparts.
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