Inflammatory Reactions in Peritonitis and Malignant Obstructive Jaundice Clinical and Experimental Studies with Special Emphasis on the Cellular Immune Response

Detta är en avhandling från Uppsala : Acta Universitatis Upsaliensis

Sammanfattning: Patients with peritonitis or malignant obstructive jaundice (HPB+) have an increased morbidity and mortality due to sepsis. An altered cell-mediated immunity in the intestinal mucosa might promote gut barrier failure, increased endotoxin and cytokine release and bacterial translocation (BT) in these conditions. A clinically relevant rat model of polymicrobial peritonitis induced sepsis by cecal ligation and puncture (CLP) was used. Septic animals demonstrated a superficial injury in the small intestinal mucosa, and a significant reduction in T lymphocytes in the villi, as well as increased number of macrophages in the villi and in the MLNs as compared to sham. CLP caused increased concentration of TNF-? and IL-6 in ascitic fluid. CLP + the immunomodulator Linomide decreased the TNF-? level, reduced mucosal damage and attenuated the changes in T lymphocytes and macrophages observed following CLP. CLP + selective cyclooxygenase (COX)-2 inhibitor (SC-236) or nonselective COX inhibitor (indometacin) decreased the amount of macrophages in the mucosa and the MLNs compared to untreated CLP. CLP + indometacin decreased T lymphocytes in the villi and MLNs. SC-236 + CLP reduced mucosal injury and cytokine release as compared to indometacin. An increased rate of apoptosis in both the mucosa and MLNs was seen following CLP; COX inhibitors enhanced this phenomenon in the MLNs.BT occurred infrequently in patients with acute peritonitis and in HPB+ there was no evidence of BT. Peritonitis and HPB+ causes significant inflammatory cellular reactions as increased endotoxin and cytokine plasma levels and an altered immune cell distribution in MLNs, in HPB+ a high rate of apoptosis in MLNs was observed. An altered pattern of immunocompetent cells within the mucosa and in MLNs was found in experimental and clinical peritonitis as in HPB+. Lymphocyte depletion may be a result of increased apoptosis, which could reduce the ability of septic or jaundice patients to eradicate infection.