Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences (FCF), University of São Paulo (USP), São Paulo, Brazil.
Universidade Paulista, São Paulo, Brazil.
Front Immunol. 2019 Jan 17;9:3165. doi: 10.3389/fimmu.2018.03165. eCollection 2018.
may provoke peritonitis and death, especially in immunocompromized individuals such as diabetic patients. We evaluated the role of insulin in -induced peritoneal infection in diabetic and non-diabetic rats. Alloxan-diabetic male Wistar rats and their respective controls received intraperitoneal injections of different strains of or sterile phosphate-buffered saline. After 3 days of infection, the first set of diabetic and non-diabetic rats received 4 and 1 IU, respectively, of neutral protamine Hagedorn insulin and were analyzed 8 h later. The second set of diabetic and non-diabetic rats received 4 and 1 IU, respectively, of insulin 2 h before intraperitoneal infection and a half dose of insulin at 5 p.m. for the next 2 days and were analyzed 16 h later. The following measurements were performed: (a) number of cells in the peritoneal lavage fluid (PeLF), white blood cell count, and blood glucose; (b) serum insulin and corticosterone; (c) cytokine levels in the PeLF; (d) expression of adhesion molecules in the vascular endothelium; and (e) microbicidal activity. Diabetic rats showed an increased number of polymorphonuclear leukocytes (PMNs) and increased concentrations of CINC-1, IL-4, and IFN-γ in the PeLF after infection with the ATCC 25923 or N315 αHL strain. The mesenteric expression of PECAM-1 was increased after infection with the N315 HLA strain. ICAM-1 expression was increased with ATCC infection. Treatment of diabetic rats with a single dose of insulin restored CINC-1 levels in the PeLF for both strains; however, PMN migration, IL-4, and IFN-γ were restored in rats infected with the ATCC strain, whereas the PeLF concentrations of CINC-2, IL-1β, and IL-4 were increased in N315-infected animals. Insulin restored PMN migration and CINC-2 levels in the PeLF in ATCC-infected rats. After multiple treatments with insulin, the levels of IL-1β, IL-6, and IFN-γ were increased in the PeLF of diabetic rats after infection with either strain, and CINC-2 levels were restored in N315-infected animals. These results suggest that insulin distinctively modulates cytokine production or release, PMN leukocyte migration, and adhesion molecule expression during the course of peritonitis induced by different strains of .
可能会引发腹膜炎和死亡，尤其是在免疫功能低下的个体中，如糖尿病患者。我们评估了胰岛素在糖尿病和非糖尿病大鼠诱导性腹膜炎感染中的作用。 链脲佐菌素诱导的糖尿病雄性 Wistar 大鼠及其相应对照大鼠分别接受不同株 或无菌磷酸盐缓冲盐水的腹腔内注射。感染 3 天后，第一组糖尿病和非糖尿病大鼠分别接受 4 和 1 IU 中性鱼精蛋白 Hagedorn 胰岛素，并在 8 小时后进行分析。第二组糖尿病和非糖尿病大鼠分别在腹腔感染前 2 小时接受 4 和 1 IU 胰岛素，并在接下来的 2 天每天下午 5 点接受半剂量胰岛素，然后在 16 小时后进行分析。进行了以下测量：（a）腹腔灌洗液（PeLF）中的细胞数、白细胞计数和血糖；（b）血清胰岛素和皮质酮；（c）PeLF 中的细胞因子水平；（d）血管内皮细胞黏附分子的表达；和（e）杀菌活性。感染 ATCC 25923 或 N315 αHL 株后，糖尿病大鼠的多形核白细胞（PMN）数量增加，PeLF 中 CINC-1、IL-4 和 IFN-γ 的浓度增加。感染 N315 HLA 株后肠系膜 PECAM-1 的表达增加。ICAM-1 表达在 ATCC 感染时增加。单次胰岛素治疗可恢复两种菌株感染大鼠 PeLF 中的 CINC-1 水平；然而，PMN 迁移、IL-4 和 IFN-γ在感染 ATCC 株的大鼠中恢复，而感染 N315 株的大鼠 PeLF 中 CINC-2、IL-1β 和 IL-4 的浓度增加。胰岛素可恢复 ATCC 感染大鼠 PeLF 中的PMN 迁移和 CINC-2 水平。经多次胰岛素治疗后，两种菌株感染的糖尿病大鼠 PeLF 中 IL-1β、IL-6 和 IFN-γ 水平升高，感染 N315 株的大鼠 CINC-2 水平恢复。这些结果表明，胰岛素在不同株 诱导的腹膜炎过程中，可显著调节细胞因子的产生或释放、PMN 白细胞迁移和黏附分子的表达。
