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-morpholino-sydnonimine (SIN-1), a nitric oxide (NO)-releasing agent, to investigate the effects of NO on cytokine synthesis and cyclic nucleotide accumulation. The cytokines interleukin-1β (IL-1β) and tumor necrosis factor α (TNF α) 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-1β and TNF α as shown earlier. Cyclic nucleotide levels remained unchanged after incubation with LPS alone. SIN-1 suppressed the LPS-induced synthesis of IL-1β, and to a minor degree of TNFα. 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.