Posted on 04/27/2009 10:02:54 AM PDT by Ernest_at_the_Beach
http://en.wikipedia.org/wiki/Cytokine_storm
I’ve heard it described like this:
Cytokine storm: our body’s sometimes not too smart. It’s like telling a housekeeper to clean your house, and she is so insanely fixated about doing a good job that she ends up ripping up the floorboards, smashing the windows and ripping down the ceiling, in her increasingly psychotic mission to clean up.
That happened with the 1918 spanish flu. Google cytokin storm. Young people have strong immune systems that viruses like this cause to over-react causing fluid build up in lungs, pneumonia, death.
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What does this background have to do with “cytokine storm”?
First it explains why it is hard to understand what “cytokine storm” means. It is a summary term for a very complicated situation. It also suggests we only have a vague idea of what is happening. This is indeed the case. Cytokine dysregulation is involved in other syndromes with symptoms much like those seen in complicated influenza (e.g., toxic shock syndrome or gram negative sepsis). In these cases the causes are more related to “always on” T-cell activation (stuck accelerator). Whether “always on” activation and thus continuous pro-inflammatory cytokine production, some other kind of cytokine dysregulation, or nothing to do with cytokines happens in influenza is still open to question. The strongest evidence comes from the clinical presentation of virulent influenza cases and the evidence in mice that infection with influenza virus carrying the HA gene from the 1918 virus seems to strongly activate some immune cells to over-produce a half dozen or more cytokines. An animation from The New England Journal article on H5N1 influenza by Mike Osterholm is meant to illustrate how a positive feedback could cause a cytokine storm, but it is only suggestive of one possibility, because we don’t know how a cytokine storm is produced in influenza (if indeed it is).
However, it is reasonable and plausible to say cytokine dysregulation might be involved in some virulent influenza infections. In desperation, clinicians have treated patients with potent anti-inflammatory drugs, usually steriods. There is no evidence that this helps. A “cytokine storm” of a more limited nature is sometimes seen in cancer chemotherapy patients, where it is treated in its earliest stages by iv. benadryl and steroids, with some success. However in these cases, there is no infectious agent involved; even if steroids worked for influenza-induced cytokine storm, they cause a general downshift of the immune system which might allow the virus to run rampant and kill the patient via ordinary viral pneumonia. In ordinary infection-related sepsis, steroids are shown to slightly increase mortality (Crit Care Med. 1995 Aug;23(8):1430–9.) This is but one of the complicating considerations that clinicians will have to navigate during an outbreak. An isolated study showed that in children with central nervous system (brain) symptoms—an early sign of cytokine storm—due to (human, not H5N1) influenza infection, mild and controlled reduction in body core temperature (hypothermia) seems to reduce damage to brain cells as well as reducing the progression to a full-blown cytokine storm and multi-organ failure. (Pediatrics International Volume 42 Issue 2 Page 197 - April 2000.)
In 2003, researchers at Imperial College London tested a drug that interferes with a “survival signal” that keeps activated T-cells working at the site of inflammation during influenza infection in mice. The signal, another cytokine designated OX40, essentially disables the brakes on the T-cell response. By blocking the OX40 receptor on T-cells, researchers were able protect mice from the serious symptoms of virulent flu (paper in J. of Experimental Medicine and reported in New Scientist). The drug, to be made by a company called Xenova Research, was supposed to be in phase I clinical trial in 2004, but we have no further information of its status (additional information solicited for this entry).
Cytokine Storms
Venky Ramakrishna, International Society For Inerferon and Cytokine Research Jan 2006 pg 7–10.
Xenova retains all rights for the use of OX40 in up-regulation whilst Genentech Inc (since 2002) and Celltech Group (bought by UCB located in Belgium in 2005) have the rights for down-regulation. (maybe we should contact these companies and ask what is being done with these rights.)
Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells Respiratory Research 2005, 6:135 Published Nov 2005
Cytokine Storm and the Influenza Pandemic
Angela L. Petrosino, M.P.H., Medical College of Ohio
Inflammatory Response Current Concepts
Edward R. Sherwood, MD, 56th Annual Referesher Course Lectures and Basic Science Reviews American Society of Anesthesiologists, 7 pgs
Cytokine Storm on Wikipedia
Horst Ibelgrauft’s Cytokines & Cells Online Pathfinder Encyclopaedia (COPE)
18,000+ entries/pages | 48,800+ references | 215,500+ internal hyperlinks
Cytokine tutorial
Dept of Veterinary Science and Microbiology, University of Arizona
Cell Interactions Cytokines
Immunology Division, Department of Pathology, Cambridge University
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Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis. They must be produced de novo in response to an immune stimulus. They generally (although not always) act over short distances and short time spans and at very low concentration. They act by binding to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter its behavior (gene expression). Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokine receptors), proliferation, and secretion of effector molecules.
Cytokine is a general name; other names include lymphokine (cytokines made by lymphocytes), monokine (cytokines made by monocytes), chemokine (cytokines with chemotactic activities), and interleukin (cytokines made by one leukocyte and acting on other leukocytes). Cytokines may act on the cells that secrete them (autocrine action), on nearby cells (paracrine action), or in some instances on distant cells (endocrine action).
It is common for different cell types to secrete the same cytokine or for a single cytokine to act on several different cell types (pleiotropy; see the table below.) Cytokines are redundant in their activity, meaning similar functions can be stimulated by different cytokines. Cytokines are often produced in a cascade, as one cytokine stimulates its target cells to make additional cytokines. Cytokines can also act synergistically (two or more cytokines acting together) or antagonistically (cytokines causing opposing activities).
Their short half life, low plasma concentrations, pleiotropy, and redundancy all complicated the isolation and characterization of cytokines. Searches for new cytokines is now often conducted at the DNA level, identifying genes similar to known cytokine genes.
Cytokine activities are characterized using recombinant cytokines and purified cell populations in vitro, or with knock-out mice for individual cytokine genes to characterize cytokine functions in vivo. Cytokines are made by many cell populations, but the predominant producers are helper T cells (Th) and macrophages.
The largest group of cytokines stimulates immune cell proliferation and differentiation. This group includes Interleukin 1 (IL-1), which activates T cells; IL-2, which stimulates proliferation of antigen-activated T and B cells; IL-4, IL-5, and IL-6, which stimulate proliferation and differentiation of B cells; Interferon gamma (IFNg), which activates macrophages; and IL-3, IL-7 and Granulocyte Monocyte Colony-Stimulating Factor (GM-CSF), which stimulate hematopoiesis.
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Selected Immune Cytokines and Their Activities*
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Added some updates.
Ironically, the healthy immunse system overreacts and kills them.
bump, thanks for the post.
Thanks ,....
Cock Fighting is a major sport in Mexico. Assume they were fighting in a barn where there were pigs and a hat dance going at the same time.
fyi
Google map to track Flu Hot Spots
fascinating bump
How come we don’t see this in the Mid East and Asia...not including Australia...?
This can only happen when pigs fly.
(Sorry, I couldn’t resist.)
I think it might have to do with the incubation time , & if they visited Mexico. New Zealand does have confirmed cases..
Suspected case in ISRAEL: While the influenza is generally on decline in Israel, the country’s health minister reported the first suspected case of swine flu in Israel http://www.ynetnews.com/articles/0,7340,L-3706679,00.html
Thanks Ernest.
Mexico: 149 suspected deaths from swine flu - 26 confirmed cases
United States: 40 confirmed cases
Canada: 6 confirmed cases
Spain: 1 confirmed case
UK, Spain, Israel, Brazil, Australia and New Zealand: suspected cases being tested
Australia does have suspected cases ...
Also there isn’t alot of news being reported about the South Carolina private school which is closed because of suspected swine flu . Some students at the school went to Mexico on Spring Break...
But if you search the web you can find the article...
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