• L M Napolitano and C Campbell.
• Department of Surgery, University of Massachusetts, Worcester.
• Arch Surg Chicago. 1994 Dec 1;129(12):1276-82; discussion 1282-3.

ObjectiveTo examine the effect of nitric oxide inhibition on cytokine production and immunologic function in a murine thermal-injury and an alcohol (ETOH)-ingestion model.DesignRandomized controlled experiment.SettingUniversity surgical research laboratory.AnimalsForty male Balb/C mice.InterventionsAnimals were randomized to four groups: normal saline solution-sham (NS-sham), ETOH-sham, NS-burn, and ETOH-burn. Animals received 20% ETOH or NS daily for 14 days by gavage. A 20% full-thickness burn was induced 4 hours after the last dose of ETOH or NS was administered. Animals were killed 4 days after the burn was induced.Main Outcome MeasuresSplenocytes were harvested and stimulated with the mitogens lipopolysaccharide or concanavalin A. These mitogen-stimulated splenocyte cultures had the addition of exogenous N-monomethyl-L-arginine (2.5 or 10 micrograms/mL), a nitric oxide synthase inhibitor. Splenocyte production of interleukin-10 (IL-10), interferon-gamma, nitrite, and prostaglandin E2 were measured, and lymphocyte proliferative response was examined.ResultsInterleukin-10 and interferon-gamma production were significantly suppressed in thermal injury, and lymphocyte proliferative response was markedly reduced. Exogenous N-monomethyl-L-arginine normalized splenocyte IL-10 production in a dose-dependent manner in NS-burn and ETOH-burn groups, improved lymphocyte proliferative response, and significantly decreased splenocyte nitrite production. Interferon-gamma release was not up-regulated by N-monomethyl-L-arginine.ConclusionsThermal injury is associated with a suppression of splenocyte IL-10 production and lymphocyte proliferative response. Inhibition of nitric oxide synthesis normalized IL-10 production and significantly improved splenocyte proliferative response. These data suggest that nitric oxide is an important modulator of cytokine regulation and immunologic function in thermal injury, thereby ultimately influencing host defense.

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