Study: Calming the Cytokine Storm

[indigo girl]

http://afludiary.blogspot.com/2011/09/study-calming-cytokine-storm.html

I think that this research will turn out to be of tremendous importance. Watching the short video of the researchers themselves , I was struck by how very calmly these two scientists talk about their work. They must know how amazing this all could be, and how many lives could be saved by this completely different approach to treatment of severe influenza cases. This is really BIG. All of those people who died of multi organ failure from bird flu, all those pregnant women who died during the swine flu pandemic, I think of them and wish that this research was further along, and that they could have benefited from it. Most of them were so young, and they should not have died from influenza but they did because of cytokine storm and the cascade effect on their organs.

I know that I have written before on cytokine storm and how devasting it is for the victim. I am simply blown away by the very thought of preventing this from happening.

Please check out the video attached to the link. It's a very brief and elegant explanation of their work. Hats off to them, and to Scripps! Well done!

Researchers at The Scripps Research Institute have found a novel mechanism by which certain viruses such as influenza trigger a type of immune reaction that can severely sicken or kill those infected.

This severe immune reaction--called a "cytokine storm"--floods the tiny air sacs of the lungs with fluid and infection-fighting cells, blocking off airways and damaging body tissues and organs. Cytokine storms are believed to have played a major role in the staggering mortality of the 1918-1919 worldwide influenza pandemic, as well as in the more recent swine flu and bird flu outbreaks.

(A hugh thank you to Mike at Avian Flu Diary for posting the explanations regarding this. You must have known that I would be using this, it's so very, very important!)

[indigo girl]

This is what Cytokine Storm can do:

http://scienceblogs.com/effectmeasure/2006/10/a_cautionary_tale_about_cytoki.php

The following is from an old post written in October 2006 at Effect Measure about a drug trial gone wrong. Read the full link to learn exactly what happened to these men and what that "severe inflammation" did to them.

...it worked to dramatically reduce the effects of autoimmune disease in two animal models. The autoimmune process in these diseases is not the same as cytokine storm, except that it is the result of an over active immune system. The objective was to calm the activity of the immune system, and that seemed to work in animals.

In the spring of this year the drug was tested on humans. Six subjects received doses of the drug lower than given the animals because this was a safety trial. This is what happened:

Around 60 to 90 minutes after the men received their injections, their bodies were flooded by a surge of inflammatory chemicals called cytokines, which combat severe infections like those seen in patients with blood poisoning. The cytokines caused severe inflammation.

[indigo girl]

David and Goliath: How one cytokine may take down influenza

http://www.virology.ws/2011/10/07/david-and-goliath-how-one-cytokine-may-take-down-influenza/

Even though you won't hear at the workplace about anything else other than flu vax or Tamiflu (after being infected, usually) that might be effective against influenza, this research has to be pointing in the right direction. This folks, is the wave of the future. And, none too soon because what we are doing now does not always work. We need this before the next pandemic hits which event certainly will occur in the not too distant future. Someday soon, I fervently hope, this will be big news, and if we are lucky,before we lose our current antiviral treatment, Tamiflu the way we lost amantadine. Everyone is aware already that the previous H1N1 strain of flu was resistant to Tamiflu? Did you know that right from the beginning of the swine flu pandemic, there were already strains resistant to it as well. That situation will only get worse. We need something really new. Just maybe, this is it.

Recent research has suggested a new method of flu prevention and treatment: the administration of granulocyte macrophage-colony stimulating factor (GM-CSF) to the lungs of mice significantly reduced flu symptoms and prevented mortality after a lethal dose of influenza virus. GM-CSF helps the body defend against the virus by boosting the presence of alveolar macrophages (AM), which are essential parts of innate defense.

Currently, there are two main methods of flu prevention and treatment: vaccines and antivirals. Vaccines work by priming the adaptive immune system against antigens in the virus from the preceding flu season (specifically, hemagglutinin and neuraminidase). They are, however, limited by the frequent genetic mutations in the influenza genome that cause antigenic drift, which in turn reduces vaccine potency. Additionally, an individual exposed to the virus not long before or after vaccination may still get sick. Antivirals for influenza mimic sialic acid, which is a natural ligand of neuraminidase, and effectively prevent newly-created virus particles getting “un-stuck” from the cellular membrane. However, in order for antivirals to be effective against flu, they must be administered within 48 hours after infection. Further, the efficacy of influenza antivirals, such as in the case of Tamiflu, can be reduced by drug-resistant strains of the virus.

GM-CSF therapy has several advantages over current methods of dealing with influenza. Unlike vaccines, GM-CSF does not rely on the body being able to mount an adaptive immune response to the virus, and treatment is not strain-specific. Mice in the experiment were first infected with PR8 H1N1, a laboratory strain, and in subsequent trials with three other strains (H3N2 HK68, and mouse-adapted H1N1 California/04/09 2009 pandemic strain). GM-CSF in the lung protected against all of these strains. The results of the tests were also unambiguous: every SPC-GM mice, which only expressed GM-CSF in the lungs, survived, while all the mice expressing no GM and the wild type mice died. Additionally, it is unlikely that viruses will develop immunity to GM-CSF, which presents a constant problem in antiviral treatment.

[lamazeteacher]

Indigogirl:

I'm interested in the use of the new program CDC has, dog kidneys to produce non allergic vaccine. What do you know about it? Are you still doing work regarding the current practice regarding flu incidence?

[eagle78]

Great post Indigo Girl, I realize this is three years old and you probably will not see this post but I found it interesting that I was just reading an article about the cytokine storm and it mentioned the clinical trial you did, where an antibody against CD28 caused the situation you mentioned, and the article also mentioned an earlier incident where a lab worker intentionally injected a large dose of bacterial endotoxins and went into septic shock as a result of the cytokine storm.

At any rate thanks for your post.