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Cytokine Storm

One of the prevailing hypotheses on why pandemic flu is so deadly is the notion that those with stronger immune systems will be more likely to die from the virus because of a "cytokine storm". The cytokine storm is thought to cause death not from the virus itself, but the immune system overreacting to it. Victims suffer a virus induced response of the immune system-"a cytokine storm"-which leads to acute respiratory distress. In otherwords, in the process of fighting the disease, a person's immune system severely damages the lungs, which likely results in death. A severe "cytokine storm" can flood and clog the lung's alveoli with infection-fighting cells, making it so oxygen can no longer be properly absorbed by the body.

Not all investigators agree with the "cytokine storm" interpretation. Studies of the time to death from the onset of influenza symptoms during the 1918 pandemic in military and civilian populations find a median time to death of 7-11 days. These data support the idea that the deaths may be predominantly due to bacterial superinfection after the acute phase of influenza. The distribution of time from onset of illness to death due to influenza-related pneumonia in 1918 are quite similar compared with time to death due to untreated pneumococcal pneumonia in the 1920s and 1930s. Other studies suggest a more complext course, in which the synergistic effects of infection with the virus, aberrant immune responses to the virus, and secondary opportunistic bacterial pneumonias were severe and often fatal.

Cytokines are chemicals released by cells that allow them to communicate with each other. Cyto means cell and kin- means kinesis or movement. Cytokines are a large family of more than 100 small proteins that function as short-range mediators involved in essentially all biological processes. Cytokines are low molecular-weight hormone-like proteins and peptides that act as communicators between cells. They can relay messages between cells, telling them to grow, stop growing, move to a trouble spot, or otherwise change the cell's function. Cytokines are important biological mediators that regulate immune and inflammatory responses. Cytokines are diverse and potent chemical messengers secreted by the cells of your immune system. They are the chief communication signals of T cells. Cytokines include interleukins, growth factors, and interferons.

These molecules, previously also termed interleukins, interferons, growth factors, and TNFs, among other designations, are involved in essentially every important biological process, from cell proliferation to inflammation, immunity, migration, fibrosis, repair, and angiogenesis. Lymphocytes, including both T cells and B cells, secrete cytokines called lymphokines, while the cytokines of monocytes and macrophages are dubbed monokines. Many of these cytokines are also known as interleukins because they serve as a messenger between white cells, or leukocytes. Interferons are naturally occurring cytokines that may boost the immune system.

When cytokines attract specific cell types to an area, they are called chemokines. These are released at the site of injury or infection and call other immune cells to the region to help repair damage and defend against infection. Binding to specific receptors on target cells, cytokines recruit many other cells and substances to the field of action.

The pandemic flu virus can trigger levels of inflammatory cytokines and chemokines that are more than 10 times higher than those that occur during a bout of the common flu. This massive increase in cytokine and chemokine activity can inflame airways, making it hard to breathe. It also contributes to the unusual severity of the pandemic flu, which can result in life-threatening pneumonia and acute respiratory distress.

One of the great unsolved mysteries surrounding the 1918 pandemic is why it tended to kill the young and healthy. Unlike yearly influenza epidemics, in which death rates are highest among infants, the elderly and those with chronic health conditions, the 1918 influenza pandemic took its greatest toll on healthy adults between the ages of 20 and 40. One possible explanation, supported by recent studies in mice with a reconstructed version of the 1918 virus, is that an over-responsive immune system may release a "cytokine storm," or excessive amount of immune system proteins that trigger inflammation and harm the patient in the process.

Most pandemic deaths were associated with either an aggressive bronchopneumonia, in which bacteria could be cultivated from lung tissue at autopsy, or with a severe acute respiratory distress-like syndrome (ARDS) characterized by blue-grey facial discoloration and excessive fluid in the lungs. In neither case is it known whether most deaths were caused by a secondary bacterial infection or a primary viral infection.

The pandemic flu virus will probably impact young and middle-aged healthy individuals far more than normal seasonal flu, probably due to the severity of the inflammation or cytokine storm it induces in healthy lungs. Many of those who died in the 1918 influenza pandemic were young people, those with the strongest immune systems whose bodies mounted the strongest immunopathologic responses.

Because of this abnormal and obverse peak of mortality across the demographic curve, the pandemic threatens social paralysis and disruption, will have a severe impact on familial and daily care (esp. for toddlers and the elderly), have a severe impact on the functionality of industry, government, health care et al, and will generate significant issues surrounding burial practices, social gatherings, and more.

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