Effects of SIN-1 on cytokine synthesis in human mononuclear cells

H.-J. Fulle, S. Endres, B. Sinha, D. Stoll, P.C. Weber, R. Gerzer

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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.
Original languageEnglish
Pages (from-to)S113-S116
Number of pages4
JournalJournal of Cardiovascular Pharmacology
Issue numberSUPPL. 3
Publication statusPublished - 30-Mar-1991

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