Canadian scientists may have found signal for dangerous H1N1 infection

[Missouriwatcher]

"The study involved patients infected during the first pandemic waves in Spain in July and August. The team looked at different cytokine mediators. Cytokines regulate the body's immune response. They tell the body when and how to fight infections, such as bacterial and viral infections. They control the actions of white blood cells.

"The one which was most noticeable to us was interleukin 17," which has consistently been associated with inflammation and autoimmune diseases, Kelvin says. "H1N1 severe disease is really an inflammatory disease."

The study, which was fast-tracked for publication in the journal Critical Care, involved 20 hospitalized patients, half of whom were admitted to intensive care, 15 outpatients who had mild H1N1 disease, and 15 healthy "controls." The findings could potentially lead to a simple blood test to identify people at the earliest stages of infection who may go on to develop severe disease, and to a drug to treat people with severe infections."
http://www.vancouversun.com/health/...l+dangerous+H1N1+infection/2344367/story.html

 

[AlaskaDenise]

Re: Canadian scientists may have found signal for dangerous H1N1 infection

(snipped)

Functions of the IL-17 family
Numerous immune regulatory functions have been reported for the IL-17 family of cytokines, presumably due to their induction of many immune signaling molecules. Most notably, IL-17 is involved in inducing and mediating proinflammatory responses. IL-17 is commonly associated with allergic responses. IL-17 induces the production of many other cytokines (such as IL-6, G-CSF, GM-CSF, IL-1β, TGF-β, TNF-α), chemokines (including IL-8, GRO-α and MCP-1) and prostaglandins (e.g. PGE2) from many cell types (fibroblasts, endothelial cells, epithelial cells, keratinocytes and macrophages). The release of cytokines causes many functions, such as airway remodeling, a characteristic of IL-17 responses. The increased expression of chemokines attracts other cells including neutrophils but not eosinophils. IL-17 function is also essential to a subset of CD4+ T-Cells called T helper 17 (Th17) cells. As a result of these roles, the IL-17 family has been linked to many immune/autoimmune related diseases including rheumatoid arthritis, asthma, lupus, allograft rejection and anti-tumour immunity.[4]

http://en.wikipedia.org/wiki/Interleukin_17

 

[AlaskaDenise]

Re: Canadian scientists may have found signal for dangerous H1N1 infection

Interleukin-17: a novel inflammatory cytokine that bridges innate and adaptive immunity.

Yu JJ, Gaffen SL.

Department of Microbiology and Immunology, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA.

Interleukin-17 (IL-17A) is a pro-inflammatory cytokine that is primarily secreted from T lymphocytes, mediators of adaptive immunity. Recently, IL-17 was shown to be the defining cytokine of a new T helper subset termed "Th17." Discovery of the Th17 population was a groundbreaking discovery that has triggered major revisions of the prevailing paradigms in T cell biology. Although produced by T cells, IL-17 promotes expansion and recruitment of innate immune cells such as neutrophils, and also cooperates with TLR ligands, IL-1 beta, and TNF alpha to enhance inflammatory reactions and stimulate production of beta-defensins and other antimicrobial peptides. Its receptor, IL-17RA, is ubiquitously expressed and shares many features with classical innate immune receptors such as shared intracellular tail motifs and convergence on common inflammatory transcription pathways. The role of IL-17 in periodontal disease is still uncertain, since IL-17 has been shown to promote bone destruction in arthritis, but is nonetheless essential to protect the host from pathogens, including periodontopathic organisms. Recent evidence has shown that Th17 cells are more osteoclastogenic than other T helper subsets such as Th1 or Th2. Ablation of IL-17 signaling prior to onset of infection with Porphyromonas gingivalis increases susceptibility to periodontal bone loss, but this finding does not rule out the efficacy of therapeutic inhibition of IL-17 after onset of severe disease. IL-17 sits at the center of many complex diseases that integrate innate and adaptive immune mechanisms and requires careful study to maximize host protective effects and minimize host deleterious effects.

PMID: 17981535 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/17981535?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_RA&linkpos=3&log$=relatedreviews&logdbfrom=pubmed

 

[Gert van der Hoek]

Re: Canadian scientists may have found signal for dangerous H1N1 infection

Link to abstract of the study of Spanish and Canadian scientists:

http://www.flutrackers.com/forum/showthread.php?p=328992#post328992

This is very interesting, I thought it would attract more attention.

May be a clue why so many have a mild H1N1 and some a virulent one.

I remember another study - from Australia I think - they found the levels of some protein are low in ICU patients.

May be in the same line?

I'll try to find it later.

 

[gsgs]

Re: Canadian scientists may have found signal for dangerous H1N1 infection

is it linked to Argentina,225(H3) mutations, Ukraine , lung-infection ?

 

[Gert van der Hoek]

Re: Canadian scientists may have found signal for dangerous H1N1 infection

In Australia researchers found low levels of an antibody called IgG2 in ICU patients.

http://www.flutrackers.com/forum/showthread.php?t=125480

http://www.flutrackers.com/forum/showthread.php?p=256326&highlight=IgG2#post256326

Now an important role of "IL-17".

According to this article (and others) IL-17 and IgG2 are related:

IL-17 deficiency suppressed anti-CII IgG2a levels

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755626/


Conclusion regarding IgG2 was - if I remember well - : check these levels and give immunoglobulin if necessary.

See also website on immunedisease, lot of information: http://www.immunedisease.com/patients-and-families/about-pi/types-of-pi/igg-subclass-deficiency.html

 

[gsgs]

Re: Canadian scientists may have found signal for dangerous H1N1 infection

it's still rather mild, so whatever they find, it should be more
dangerous in other flu

better ask: what made the 2009 pandemic so mild ?

 

[Gert van der Hoek]

Re: Canadian scientists may have found signal for dangerous H1N1 infection

Some background on "IL-17"

An Overview of IL-17 Function and Signaling

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582446/

a snip:

7. Implications for therapy

Anti-cytokine therapy for treating autoimmunity has been extremely successful. Interestingly, most of anti-cytokine drugs currently in use impact the Th17 pathway, even though they were developed before its discovery (reviwed in [52]).

The discovery of the central role of IL-17 and autoimmune disease has naturally stimulated development of antibodies against IL-17 or IL-17RA as well as IL-23 [62].

Understanding the functional role of IL-17 in various forms of disease will be critical for optimal targeting of this cytokine for effective use in therapy.

 

[kiwibird]

Re: Canadian scientists may have found signal for dangerous H1N1 infection

Published online: 17 May 2008
Abstract Statins? recently discovered anti-inflammatory effects place them at the forefront of the new therapies for chronic inflammatory and autoimmune diseases. Our recent study demonstrated that simvastatin exerts an independent immunomodulatory effect on the human monocytes and CD4+ cells. In addition to the statin-mediated effect on the monocyte cytokine production, which regulates Th17 cell differentiation, simvastatin directly inhibits IL-17 production in CD4+ cells, which may collectively inhibit the autoimmune response in multiple sclerosis (MS), a central nervous system (CNS) inflammatory demyelinating disease.

http://www.springerlink.com/content/l46068p2040r32k0/

 

[AlaskaDenise]

Re: Canadian scientists may have found signal for dangerous H1N1 infection

it's still rather mild, so whatever they find, it should be more
dangerous in other flu

better ask: what made the 2009 pandemic so mild ?

Given that influenza and other pathogens interact with immune systems in a wide variety of ways to accomplish their goal to persist, we can say 2009 H1N1 might be exploiting a slightly different pathway than other influenzas.

As I posted here, there are approximatly 120 different forms of primary immunodeficiency (including low IgG2s) for influenza to utilize.

For example, if we take selective IgA deficiency, which is present in about 1 in 300 people, use an H1N1 attack rate of 50%, and you could speculate that 1 of every 150 people should have a severe case of H1N1. Add various other factors to further refine degrees of severity.

The most important point I take from this story, is that we need to study host response far more, in addition to viral characteristics.

.

 

[Emily]

Re: Canadian scientists may have found signal for dangerous H1N1 infection

Here's another article on this interesting research.

http://www.healthzone.ca/health/news...to-molecule-17
Key to H1N1 puzzle? Look to molecule 17

December 16, 2009
Joseph Hall

Health Reporter

Why did H1N1 cause some to develop pneumonia and die while leaving most with only mild flu symptoms?

The answer might lie in the elevated presence of a single molecule in those who suffered most from the virus, according to international research led by Toronto scientists.

"We've been doing this for many years and this is the first real clue we've had between severe and mild illness," says Dr. David Kelvin, head of experimental therapeutics at Toronto's University Health Network.

"It's the first thing we can put our finger on and actually say 'this is an area (where) we should intensify our research efforts,'" said Kelvin, the senior study author.

The molecule, known as interleukin 17, may be the culprit causing severe symptoms in a host of seasonal influenzas and other respiratory ailments like SARS, he said....