Synergistic stimulation of nitric oxide hemoglobin production in rats by recombinant interleukin 1 and tumor necrosis factor.

Nitric oxide (NO) is formed from arginine in Escherichia coli lipopolysaccharide (LPS) treated rat; however, none of specific cytokine inducing NO generation is yet determined. We studied the effect of interleukin 1 (IL-1) and tumor necrosis factor (TNF) on NO production in rats by detecting NO-hemoglobin in their blood, using electron spin resonance. Either IL-1 or TNF alone stimulated NO-hemoglobin formation. Combined administration of IL-1 and TNF markedly enhanced NO-hemoglobin generation, demonstrating the synergistic character of both stimuli on NO production. Further, LPS and TNF in combination were more potent stimulator of NO-hemoglobin production in rats than each alone.