| What is a Cytokine Storm? | | | | infection (designated a type A, subtype "H1N1" virus) |
| by Steven P. Petrosino, Ph.D. and Angela L. | | | | may have been the cause of high lethality seen in the |
| Petrosino, MPH | | | | influenza pandemic of 1918 to 1919. The great |
| A cytokine storm, also called "systemic inflammatory | | | | influenza pandemic was the most destructive |
| response syndrome" (SIRS) is the systemic | | | | pandemic in recorded world history, and killed more |
| expression of a healthy and vigorous immune system | | | | people (estimated between 20 to 50 million) than all |
| resulting in the release of more than 150 | | | | casualties resulting from the first World War. |
| inflammatory mediators (cytokines, oxygen free | | | | Although the Spanish Flu pandemic affected an |
| radicals, and coagulation factors). Both | | | | enormous percentage of the world wide population |
| pro-inflammatory cytokines (such as Tumor Necrosis | | | | (up to 20% of the world population according to |
| Factor-alpha, InterLeukin-1, and InterLeukin-6) and | | | | some sources), and killed between 20 and 50 million |
| anti-inflammatory cytokines (such as interleukin 10, | | | | persons, no more than 5% of the people who |
| and interleukin 1 receptor antagonist) are elevated in | | | | contracted the Spanish Flu died (Brown et. al |
| the serum, and the fierce and often lethal interplay | | | | reported the highest death rate in India at 50 deaths |
| of these cytokines is referred to as a "Cytokine | | | | per 1000 persons contracting the disease, or a five |
| Storm". The primary contributors to the cytokine | | | | percent fatality rate). After 218 human cases of |
| storm are TNF-a (Tumor Necrosis Factor-alpha) and | | | | avian influenza (bird flu) have been confirmed |
| IL-6 (Interleukin-6). The cytokine storm is an | | | | world-wide (as of May, 2006), the lethality rate |
| inappropriate (greatly exaggerated) immune response | | | | stands at 57%. Should this strain develop into a |
| that is caused by rapidly proliferating and highly | | | | pandemic, and should it keep its current mortality |
| activated T-cells or natural killer (NK) cells. These cells | | | | rate, it has the potential to be 10 times more lethal |
| are themselves activated by infected macrophages. | | | | than the 1918 pandemic.Is the World Health |
| The cytokine storm must be treated and suppressed | | | | Organization Adequately Defending against a Potential |
| or lethality can result. | | | | Pandemic of Avian Influenza |
| | | | Avian Influenza (also called the "Bird flu") currently is |
| Acute respiratory viral infection results in a cytokine | | | | 10 times more lethal than the strain of Spanish Flu |
| storm effecting the lungs, and subsequent damage | | | | that caused the great influenza pandemic of 1918 and |
| to alveoli and lung tissue results in the lethality seen in | | | | killed up to 50 million people world-wide, and it could |
| more severe flu viral infections, especially those | | | | become the most lethal flu pandemic of all history if |
| fatalities among young healthy adults. | | | | the virus mutates allowing it to be more easily |
| | | | passed from person to person. Bird Flu patients die |
| In the absence of prompt medical intervention to | | | | from acute respiratory distress syndrome (ARDS) |
| stop the "cytokine storm", the lung will suffer | | | | caused by the "cytokine storm", and NOT directly |
| permanent damage. Many of these patients will | | | | from the virus. Neuraminidase inhibitors (i.e. Tamiflu, |
| develop acute respiratory distress syndrome (ARDS), | | | | Relenza) are not proven effective for bird flu |
| i.e. will present with pulmonary edema that is not | | | | patients, although they have been recommended by |
| caused by volume overload, or a depressed left | | | | the World Health Organization for this use, are |
| ventricular function. Deaths will usually result from | | | | currently used to treat almost all bird flu patients, and |
| multisystem organ failure, and not from lung failure. | | | | are being stockpiled by governments world-wide |
| Sepsis, Viral Infections, and Cytokine StormSepsis is | | | | (including the United States) to treat a potential |
| a severe systemic inflammatory response and is one | | | | pandemic should the avian influenza virus undergo a |
| example of a pathologic condition associated with | | | | final mutation which would allow it to be more easily |
| "cytokine storm". Sepsis is an often lethal | | | | passed from person to person. A treatment to |
| hemodynamic collapse which is usually the result of a | | | | prevent or reduce the autoimmune reaction (cytokine |
| super infection by gram-negative bacterial endotoxins. | | | | storm) associated with the bird flu is commercially |
| Sepsis is also classified as septic shock syndrome | | | | available by prescription, but is not currently being |
| (SSS).Cytokine storm can also result from viral | | | | recommended by the World Health Organization to |
| infections such as influenza, and an exaggerated | | | | treat these patients. |
| systemic immune response to that particular viral | | | | |