Herfarth H H, Böcker U, Janardhanam R, Sartor R B
Center for GI Biology and Disease, University of North Carolina, Chapel Hill, North Carolina, USA.
Gastroenterology. 1998 Oct;115(4):856-65. doi: 10.1016/s0016-5085(98)70257-4.
BACKGROUND & AIMS: Interleukin (IL)-10, which inhibits macrophages and T-helper lymphocyte type 1 (TH1) lymphocytes, attenuates chronic granulomatous inflammation induced by bacterial cell wall polymers. This study determines whether corticosteroids enhance the protective effects of IL-10 in cultured peripheral blood mononuclear cells (PBMNCs) and in vivo when started before or after the onset of experimental chronic granulomatous inflammation.
Intestines of Lewis rats were injected intramurally with streptococcal peptidoglycan-polysaccharide (PG-APS) polymers. Daily murine recombinant IL-10 and/or dexamethasone (DEX) therapy was started 12 hours before or at several intervals after PG-APS injection.
IL-10 plus corticosteroids additively inhibited IL-1beta secretion in human PBMNCs but preserved the beneficial IL-1RA/IL-1beta ratio induced by IL-10. IL-10 started before PG-APS injection significantly attenuated intestinal and extraintestinal inflammation, with even more pronounced effects in combination with subtherapeutic doses of DEX. The combination of DEX decreased the effective dose of IL-10 by at least one half. After onset of systemic inflammation using doses effective for prevention, IL-10 monotherapy had nearly no benefit and DEX plus IL-10 was similar to the mild therapeutic effect of DEX alone.
The combination of IL-10 and corticosteroids allows lower doses of both agents in preventing chronic intestinal and systemic inflammation. However, timing of IL-10 administration is a critical variable in regulating inflammation.
白细胞介素（IL）-10可抑制巨噬细胞和1型辅助性T淋巴细胞（TH1），减轻细菌细胞壁聚合物诱导的慢性肉芽肿性炎症。本研究旨在确定在实验性慢性肉芽肿性炎症发作之前或之后开始使用皮质类固醇是否能增强IL-10在体外培养的外周血单核细胞（PBMNC）和体内的保护作用。
向Lewis大鼠肠壁内注射链球菌肽聚糖-多糖（PG-APS）聚合物。在PG-APS注射前12小时或注射后的几个时间点开始每日给予小鼠重组IL-10和/或地塞米松（DEX）治疗。
IL-10加皮质类固醇可相加性抑制人PBMNC中IL-1β的分泌，但保留了IL-10诱导的有益的IL-1RA/IL-1β比值。在PG-APS注射前开始使用IL-10可显著减轻肠道和肠道外炎症，与亚治疗剂量的DEX联合使用时效果更明显。DEX的联合使用使IL-10的有效剂量降低了至少一半。在使用有效预防剂量引发全身炎症后，IL-10单一疗法几乎没有益处，DEX加IL-10的效果与单独使用DEX的轻度治疗效果相似。
IL-10和皮质类固醇联合使用可降低两种药物的剂量以预防慢性肠道和全身炎症。然而，IL-10给药的时机是调节炎症的关键变量。
