Napolitano L M, Campbell C
Department of Surgery, University of Massachusetts, Worcester.
Arch Surg. 1994 Dec;129(12):1276-82; discussion 1282-3. doi: 10.1001/archsurg.1994.01420360066008.
To examine the effect of nitric oxide inhibition on cytokine production and immunologic function in a murine thermal-injury and an alcohol (ETOH)-ingestion model.
Randomized controlled experiment.
University surgical research laboratory.
Forty male Balb/C mice.
Animals 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.
Splenocytes 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.
Interleukin-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.
Thermal 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.
在小鼠热损伤和酒精摄入模型中，研究一氧化氮抑制对细胞因子产生和免疫功能的影响。
随机对照实验。
大学外科研究实验室。
40只雄性Balb/C小鼠。
动物被随机分为四组：生理盐水假手术组（NS-假手术组）、酒精假手术组、生理盐水烧伤组和酒精烧伤组。动物通过灌胃每天接受20%酒精或生理盐水，持续14天。在最后一剂酒精或生理盐水给药4小时后，诱导20%的全层烧伤。烧伤诱导4天后处死动物。
收获脾细胞，并用脂多糖或伴刀豆球蛋白A刺激。这些经丝裂原刺激的脾细胞培养物中添加了外源性N-甲基-L-精氨酸（2.5或10微克/毫升），一种一氧化氮合酶抑制剂。测定脾细胞白细胞介素-10（IL-10）、干扰素-γ、亚硝酸盐和前列腺素E2的产生，并检测淋巴细胞增殖反应。
热损伤中白细胞介素-10和干扰素-γ的产生显著受抑制，淋巴细胞增殖反应明显降低。外源性N-甲基-L-精氨酸使生理盐水烧伤组和酒精烧伤组的脾细胞IL-10产生呈剂量依赖性恢复正常，改善淋巴细胞增殖反应，并显著降低脾细胞亚硝酸盐产生。N-甲基-L-精氨酸未上调干扰素-γ释放。
热损伤与脾细胞IL-10产生受抑制和淋巴细胞增殖反应有关。一氧化氮合成的抑制使IL-10产生恢复正常，并显著改善脾细胞增殖反应。这些数据表明，一氧化氮是热损伤中细胞因子调节和免疫功能的重要调节因子，从而最终影响宿主防御。
