This year’s deadly flu epidemic has led to a lot of questions of why we are seeing cardiac arrhythmias, myocardial infarctions, airway swelling, and increased deaths.  What is even more alarming is that these events are occurring in relatively young people.

One of the the theories being put forth is that this is being caused by a “cytokine storm.”  This is not a new theory (dating back to 1993) but not something many physicians have heard about.  Cytokines signal immune cells like T-cells and macrophages to go to sites of infections.   Cytokines include tumor necrosis factor-alpha, interleukin-1, interleukin-6 and coagulation factors. There is usually a feedback loop that limits the response.  Sometimes, this doesn’t appropriately occur and an exaggerated response occurs called a cytokine storm.   The theory is that this is a response to a new and highly pathologic virus or organism.  This response requires a very healthy immune system.and therefore spares the extremes of age and those with impaired immune responses.

Cytokine storm also known as cytokine cascade or hypercytokinemia is thought to be fatal accelerated chain reaction between cytokines and white blood cells.   Symptoms include fever, swelling, nausea, extreme fatigue, and vasocclusive symptoms including chest pain.

Cytokine storms may occur in many life threatening conditions like ARDS, Ebola, smallpox, SIRS, and sepsis.  Some medications may also cause the condition as well as graft vs host disease and pancreatitis.


Many believe that cytokine storms were responsible for the disproportionate number of healthy young adult deaths during the 1918 influenza pandemic, the SARS epidemic of 2003, the H5N1 epidemic, the hantavirus syndromes, and even EBOLA outbreaks.

The good news is there are possible directed treatments for cytokine storm being developed including experimental agents like OX40-Ig (which work to stop the Tcell response)

Other medications have theoretical or limited literature support that should be considered include

  1. ACE Ibhibitors and angiotensin II receptor blockers (particularly in pulmonary cases)
  2. Gemfibrozil has limited studies that show its effectiveness in treating H5N1 although administered intraperitoneally
  3. Anti-oxidants
  4. TNF-alpha blockers (anti-arthritis medicines)

Interestingly, corticosteroids have shown no benefits in cytokine storm.




Source: The cytokine storm of severe influenza and development of immunomodulatory therapy