Ziesché E, Scheiermann P, Bachmann M, Sadik C D, Hofstetter C, Zwissler B, Pfeilschifter J, Mühl H
Pharmazentrum Frankfurt/ZAFES, Intensive Care Medicine and Pain Therapy, University Hospital Goethe University, 60590 Frankfurt am Main, Germany.
Clin Exp Immunol. 2009 Sep;157(3):370-6. doi: 10.1111/j.1365-2249.2009.03969.x.
Interleukin (IL)-22 production triggered by innate immune mechanisms has been identified as key to efficient intestinal anti-bacterial host defence and preservation of homeostasis. We hypothesized that glucocorticoid therapy may impair IL-22 expression, which should promote intestinal epithelial damage with the potential of subsequent bacterial translocation. High-dose corticosteroid therapy in Crohn's disease has been associated with an increased rate of abscess formation and ultimately with a higher risk of developing postoperative infectious complications, including abdominal sepsis. Thus, we sought to investigate effects of the prototypic glucocorticoid dexamethasone on IL-22 production in the context of bacterial infection. Enhanced IL-22 plasma levels were detectable in rat sepsis. Moreover, heat-inactivated Staphylococcus epidermidis, used as a prototypic activator of innate immunity, induced robust production of IL-22 by human peripheral blood mononuclear cells (PBMC). Here, we report for the first time that dexamethasone mediates remarkable suppression of IL-22 as detected in S. epidermidis-activated PBMC and rat sepsis, respectively. The data presented herein suggest that insufficient IL-22 function may contribute to impaired intestinal host defence in the context of corticosteroid therapy.
由先天免疫机制触发的白细胞介素(IL)-22生成已被确定为有效的肠道抗菌宿主防御和维持内环境稳定的关键。我们推测糖皮质激素治疗可能会损害IL-22的表达,这会促进肠道上皮损伤并可能导致随后的细菌易位。克罗恩病的高剂量皮质类固醇治疗与脓肿形成率增加有关,并最终导致术后感染并发症(包括腹部脓毒症)的风险更高。因此,我们试图研究在细菌感染情况下,典型糖皮质激素地塞米松对IL-22生成的影响。在大鼠脓毒症中可检测到IL-22血浆水平升高。此外,作为先天免疫的典型激活剂,热灭活的表皮葡萄球菌可诱导人外周血单核细胞(PBMC)大量生成IL-22。在此,我们首次报告,地塞米松分别在表皮葡萄球菌激活的PBMC和大鼠脓毒症中显著抑制IL-22。本文提供的数据表明,在皮质类固醇治疗的情况下IL-22功能不足可能导致肠道宿主防御受损。