ALVEOLAR MACROPHAGES AUTOREGULATE IL-1 AND IL-6 PRODUCTION BY ENDOGENOUS NITRIC-OXIDE

The effect of nitric oxide on the lipopolysaccharide (LPS)-induced cyt okine production by alveolar macrophages was studied. When alveolar ma crophages were cultured, substantial amounts of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and nit ric oxide are produced upon stimulation with LPS. Inhibition of the ni tric oxide production by the L-arginine analogue N-G-monomethyl-L-argi nine (NMMA), resulted in an increase of IL-1 beta and IL-6, whereas th e TNF-alpha concentrations remained unchanged, suggesting specific inh ibitory effects of nitric oxide on the LPS-stimulated cytokine product ion by alveolar macrophages. The observed cytokine-modulating properti es of nitric oxide did not result from cytotoxic actions of the oxidat ion of L-arginine on macrophages, since nitric oxide synthesis did not affect the viability of the alveolar macrophages. Conversely the nitr ic oxide donor S-nitroso-N-acetyl-D, L-penicillamine (SNAP) induced do se-dependent inhibition of IL-1 production in LPS-stimulated alveolar macrophages in which endogenous nitric oxide production was blocked. T he results indicate that nitric oxide can affect the LPS-induced IL-1 beta and IL-6 secretion by alveolar macrophages in an autoregulatory w ay and are discussed in view of the important physiologic consequences this autoregulation by nitric oxide may have.