THE ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA IN ACQUIRED-IMMUNODEFICIENCY-SYNDROME

Tumour necrosis factor-alpha-(TNF) is a primary mediator in the pathogenesis of infection, tissue injury and inflammation. It is synthesised by various activated, phagocytic and non-phagoctic cells, and a wide variety of infectious or inflammatory stimulae are capable of triggering TNF biosynthesis. Recent studies indicate that overproduction of TNF in septicaemia is a critical step in triggering septic shock and multiple organ damage. Intravenous administration of recombinant human TNF induced the same types of derangement in cardiovascular homatologic, inflammatory and metabolic homeostasis that are found with endotoxic or septic shock. Chronic TNF production causes a potentially lethal syndrome of cachexia, anaemia, and protein and lipid wasting. Several investigators have recently demonstrated elevated levels of serum TNF in patients with acquired immunodeficiency syndrome (AIDS), these levels being closely correlated with the severity of the disease. This review discusses the role of TNF in the pathophysiology of AIDS and of several disorders associated with the latter. In addition, it discusses the interactions between TNF and several agents used in AIDS therapy, and suggests the use of TNF-antagonists in combination as a therapeutic regimen for AIDS patients.