A cytokine storm is a potentially fatal immune reaction consisting of a positive feedback loop between cytokines and immune cells. When the immune system is fighting pathogens, cytokines signal immune cells such as T-cells and macrophages to travel to the site of infection. In addition, cytokines activate those cells, stimulating them to produce more cytokines. Normally this feedback loop is kept in check by the body. However, in some instances, the reaction becomes uncontrolled, and too many immune cells are activated in a single place. The precise reason for this is not entirely understood. Cytokine storms have potential to do significant damage to body tissues and organs. If a cytokine storm occurs in the lungs, for example, fluids and immune cells such as macrophages may accumulate and eventually block off the air passageways. Positive feedback is a type of feedback. ... Cytokines are small protein molecules that regulate communication among immune system cells and between immune cells and those of other tissue types. ... T cells are a subset of lymphocytes that play a large role in the immune response. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ... Macrophages (Greek: big eaters) are cells found in tissues that are responsible for phagocytosis of pathogens, dead cells and cellular debris. ...

Role in pandemic deaths

It is theorized that cytokine storms were responsible for many of the deaths during the 1918 influenza pandemic, which killed a disproportionate number of young adults (a phenomenon that could repeat itself in future flu pandemics). In this case, a healthy immune system may have been a liability rather than an asset. Preliminary research results from Hong Kong also indicated this as the probable reason of many deaths during the SARS epidemic in 2003. The Spanish Flu Pandemic, also known as La Grippe Espagnole, or La Pesadilla, was an unusually severe and deadly strain of avian influenza, a viral infectious disease, that killed some 50 million to 100 million people worldwide over about a year in 1918 and 1919 [1]. It is thought to... Severe Acute Respiratory Syndrome (SARS) is an atypical form of pneumonia. ... 2003 (MMIII) was a common year starting on Wednesday of the Gregorian calendar. ...

Clinical trials of TGN1412

In March 2006, 6 men receiving the experimental drug TGN1412 suffered serious symptoms, from what may have been the effects of a cytokine storm. The company had - based on results from animal trials - claimed that TGN1412 could activate T-cells in a way that would not cause the cytokine storm one would expect based on results from other drugs working the same way. TGN1412 (also known as CD28-SuperMAB®) is the working name of an immunomodulatory drug intended for the treatment of B cell chronic lymphocytic leukemia (B-CLL) and rheumatoid arthritis. ... TGN1412 (also known as CD28-SuperMAB®) is the working name of an immunomodulatory drug intended for the treatment of B cell chronic lymphocytic leukemia (B-CLL) and rheumatoid arthritis. ...

Treatment

A 2003 report in the Journal of Experimental Medicine demonstrates the possibility of preventing a cytokine storm. A few days after T-cells are activated, they produce a molecule called OX40. OX40 binds to receptors on T-cells, preventing them from dying and increasing cytokine production. A combined protein, OX40-immunoglobulin (OX40-Ig), prevents OX40 from reaching the T-cell receptors, thus reducing the T-cell response. Experiments in mice have demonstrated that OX40-Ig can reduce the symptoms associated with an immune overreaction while allowing the immune system to fight off the virus successfully. T cells are a subset of lymphocytes that play a large role in the immune response. ...

External links

• A Critical Role for OX40 in T Cell–mediated Immunopathology during Lung Viral Infection