Cytokine mediators of septic infections in the normal and granulocytopenic host.
Cytokines presently known to be involved in systemic bacterial infection are tumour-necrosis factor (TNF), interleukin (IL)-1, IL-6, IL-8 and interferon-gamma (IFN-gamma) and the counterregulatory molecules soluble TNF receptor (sTNFR) and IL-1 receptor antagonist (IL-1 Ra). In animal models TNF, IL-1 and IFN-gamma mediate organ damage, low blood pressure and fatality, whereas IL-6 is involved in infection-related manifestations, like the production of acute-phase protein and fever, and IL-8 is chemotactic to granulocytes. TNF and IL-1 increase expression of adhesion molecules on endothelial cells and influence a number of components of the haemostatic system in favour of coagulation. The presence of cytokines in the circulation is characterized by sequential releases of TNF, IL-1 and IL-6/IL-8; however, many variations of this pattern exist during human infection. In experiments as well as in human infection TNF, IL-1, IL-6, IL-8 and IFN-gamma have been detected, and levels of TNF, IL-6 and IL-8 have been found to be associated with the severity of the disease. Collectively, TNF, IL-1 and IFN-gamma emerge as mediators of systemic infection and septic shock whereas IL-6 and IL-8 are related to other manifestations of infection. Counteracting molecules like sTNFR are released after somewhat of a delay following TNF and IL-1Ra is released concomitantly with IL-1. Probably these factors modulate the cytokine effect although their true potency in natural infection has yet to be clarified. In granulocytopenic infections TNF, IL-1, IL-6 and IL-8 can be detected in serum, and levels of TNF and IL-6 are even higher than in the normal situation in experimental animals. Antibodies to TNF inhibit bacteria-induced fatality in granulocytopenic mice. Altogether, few data related to the granulocytopenic situation are available. However, it is reasonable to believe that the altered development of granulocytopenic infections is due to changes in the cellular constitution and not to changes in cytokine production.
Waage
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A
Department of Medicine, Region Hospital of Trondheim, Norway.
Steinshamn
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S
D000380:Agranulocytosis / Q000503:physiopathology*; D000818:Animals; D001777:Blood Coagulation; D002448:Cell Adhesion; D002465:Cell Movement; D016207:Cytokines / Q000502:physiology*; D005342:Fibrinolysis; D006801:Humans; D018805:Sepsis / Q000503:physiopathology*; D012772:Shock, Septic / Q000503:physiopathology
D016207:Cytokines