Blocking interleukin-1 in sepsis

Interleukin-1 (IL-1) is a polypeptide which possesses a broad spectrum of biological activities, many of which are associated with disease. It has been studied for its ability to induce fever, sleep and anorexia, elevate prostaglandins and nitric oxide, stimulate the release of pituitary hormones, elevate hepatic acute phase proteins, increase gene expression for other cytokines and augment the proliferation of T and B lymphocytes. In addition, IL-1 increases the synthesis of collagenases and decreases the synthesis of proteoglycans, resulting in joint destruction. More recently, IL-1 has been shown to induce hypotension and upregulate endothelial cell adhesion molecules, both important parameters of the septic shock syndrome. IL-1 also possesses host defense properties. For example, pretreatment with IL-1 non-specifically reduces lethality to bacterial and fungal infections, even in the absence of circulating neutrophils. IL-1 has been given to humans in clinical trials; as increasing doses are given, IL-1 is toxic, producing gastrointestinal disturbances and hypotension. It appears that low doses of exogenously administered IL-1 may prove useful as a therapy. On the other hand, blocking the toxic effects of IL-1 may be necessary in the treatment of certain diseases. IL-1 receptor blockade has been studied in human disease including sepsis. Similar to other studies using corticosteroids, antibodies to tumor necrosis factor, bradykinin antagonists and inhibitors of platelet activating factor, clear-cut beneficial effects of IL-1 receptor blockade have not matched those demonstrated in animals.