Drug Targets Killer Cytokine Storm From Flu

[Shiloh]

Source: http://newsblaze.com/story/20090522122417mcco.nb/topstory.html

Published: May 22,2009

Drug Targets Killer Cytokine Storm From Flu
By John McCormick


Scripts Researchers say sphingosine analog AAL-R can block the immune system response triggering a "cytokine storm."

http://www.scripps.edu/news/press/012009.html

The flu causes death one of two ways - either by overwhelming the system of very young, old, or otherwise already ill individuals - this happens with the ordinary seasonal flu and the Type A H1N1 which is now spreading like wildfire.

A really dangerous influenza virus actually causes deaths among the strongest and most healthy individuals by causing the person's normal immune system to overreact and flood the lungs with fluid.

This kind of reaction causes very high mortality rates in the range of 50% or higher, as is the case with the H5N1 bird flu that the world's health agencies have been preparing for.

The current H1N1 outbreak has had a very low mortality rate, in large part because it doesn't trigger this cytokine storm and also is a close relative of an older flu strain for which many older individuals already have partial immunity.

Researchers at the La Jolla, California-based Scripts Research Institute have recently reported that the sphingosine drug directly impacts the cytokine response and therefore may be a vital tool in reducing the mortality of any new pandemic flu virus which has a high mortality rate caused by the cytokine storm.

Unlike existing drugs which attack the virus itself, this drug doesn't attempt to stop the flu infection and is therefore independent of the particular strain involved - rather it targets what is the real danger, leaving the patient time to recover on their own.

This is not important for the current H1N1 virus which is relatively harmless, but can have a significant impact on the much feared H5N1 bird flu if it ever becomes a pandemic as many researchers fear.

John McCormick is a reporter, /science/medical columnist and finance and social commentator, with 17,000+ bylined stories. Contact John through NewsBlaze.

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[St Michael]

Re: Drug Targets Killer Cytokine Storm From Flu


A critical role for the sphingosine analog AAL-R in dampening the cytokine response during influenza virus infection
Proceedings of the National Academy of Sciences
Published online before print January 21, 2009

Contributed by Michael B. A. Oldstone, December 12, 2008 (sent for review November 6, 2008)

Abstract

Pulmonary tissue damage resulting from influenza virus infection is caused by both the cytolytic activity of the virus and the host immune response. Immune-mediated injury results from T cell-mediated destruction of virus-infected cells and by release of cytokines and chemokines that attract polymorphonuclear leukocytes (PML) and macrophages to the infected site. The cytokines/chemokines potentiate dendritic cell (DC) activation and T cell expansion, which further enhances local damage. Here we report that immune modulation by local administration to the respiratory tract of sphingosine analog AAL-R significantly dampens the release of cytokines and chemokines while maintaining protective neutralizing antibody and cytotoxic T cell responses. As a result there was a marked reduction of infiltrating PML and macrophages into the lung and resultant pulmonary tissue injury. DC maturation was suppressed, which limited proliferation of specific antiviral T cells in the lung and draining lymph nodes. Further, AAL-R was effective in controlling CD8+ T cell accumulation in the lungs even when given 4 days after initiation of influenza virus infection. These data indicate that sphingosine analogs display useful potential for controlling the immunopathology caused by influenza virus.

To whom correspondence may be addressed. E-mail: hrosen@scripps.edu or mbaobo@scripps.edu

* ? 2009 by The National Academy of Sciences of the USA