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 (loke a stuck gas pedal in a car).
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).
Thanks.