Effect of linomide on gut immune cell distribution and on TNF-alpha in plasma and ascites: an experimental study in the septic rat.

Abstract

A significant reduction of the pan T lymphocytes as well as CD4+ and CD8 subsets of cells in the gut mucosa of the septic rats has previously been demonstrated. In contrast, the populations of major histocompatibility complex (MHC) class II-positive cells and macrophages increased. The aim of this study was to evaluate if the immunomodulator Linomide influenced the immune cell distribution in the small intestinal mucosa in sepsis and, furthermore, if these changes coincide with changes in the concentration of tumor necrosis factor-alpha (TNF-alpha) in plasma or ascites. Polymicrobial sepsis was induced in rats by cecal ligation and puncture (CLP). Three different experimental groups were used: CLP, Linomide p.o. + CLP, and Linomide i.p.+ CLP, with adequate controls. Specimens were taken from the small bowel for immunohistologic staining and grading of mucosal injury. The following monoclonal antibodies were used: W3/25, OX8, R73, OX6, and ED1. All slides were examined by one "blinded" examiner. Mucosal injury was graded from 0 to 5. The immunostained tissues were also analyzed by an automatic color-based image system. All controls had a normal appearance of the mucosa (grade 0-1), whereas the septic animals had a median grade of III (II-IV) mucosal injury. Linomide i.p. + CLP decreased mucosal damage to median I (0-IV, P < 0.05). Linomide had no effects on the immune cell distribution in controls. In CLP rats, a significant reduction in both CD4+ and CD8+ T lymphocytes as well as an increased number of macrophages and MHC class II-positive cells was seen in the villi as compared with sham-operated controls (P < 0.05). Linomide attenuated these changes for CD8+ and T lymphocytes and macrophages. Sepsis caused increased concentrations of TNF-alpha in portal blood and ascites 3 h from CLP induction. This increase was attenuated by Linomide.