Cytokine neutralizing strategies in experimental sepsis.
Endotoxemia and bacteremia initiate a cytokine cascade, which may be beneficial to host defense, but in its exaggerated form may be responsible for shock and death. A large amount of experimental and clinical investigation has centered on neutralizing the cytokine cascade in order to prevent the severe pathophysiologic sequelae associated with infection and sepsis. Most of the work has been focused on systemic administration of antibodies for neutralization of specific cytokines, particularly tumor necrosis factor and interleukin-1. Both biologic and fiscal obstacles have prevented this strategy of using specific antibodies from becoming clinical practice. Of the many other strategies under investigation, four are particular exciting: 1) utilization of natural cytokine antagonists, 2) strategies for increasing cytokine clearance, 3) dietary modulation of cytokine production, and 4) gene therapy of sepsis.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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Enayati
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Fong
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D002352:Carrier Proteins / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D004032:Diet; D015316:Genetic Therapy; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000494:pharmacology; D009500:Neutralization Tests; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D018805:Sepsis / Q000503:physiopathology / Q000628:therapy*; D012795:Sialoglycoproteins / Q000494:pharmacology; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000906:Antibodies; D002352:Carrier Proteins; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C069521:recombinant human tumor necrosis factor-binding protein-1