EFFECTS OF SIN-1 ON CYTOKINE SYNTHESIS IN HUMAN MONONUCLEAR-CELLS

Human peripheral blood mononuclear cells were stimulated in vitro with the bacterial endotoxin lipopolysaccharide (LPS) in the presence of 3-morpholinosydnonimine (SIN-1), a nitric oxide (NO)-releasing agent, to investigate the effects of NO on cytokine synthesis and cyclic nucleotide accumulation. The cytokines interleukin-1-beta (IL-1-beta) and tumor necrosis factor-alpha (TNF-alpha) and the cyclic nucleotides adenosine-3',5'-cyclic monophosphate (cyclic AMP) and guanosine-3',5'-cyclic monophosphate (cyclic GMP) were measured by specific radioimmunoassays. LPS induced the synthesis of IL-1-beta and TNF-alpha as shown earlier. Cyclic nucleotide levels remained unchanged after incubation with LPS alone. SIN-1 suppressed the LPS-induced synthesis of IL-1-beta, and to a minor degree of TNF-alpha. Cyclic GMP levels but not cyclic AMP levels were markedly elevated by SIN-1. Similar results were obtained with sodium nitroprusside. These findings suggest that NO, which is known to be a product of activated macrophages and monocytes, may be involved in the regulation of cytokine synthesis.