Local production of corticotropin releasing hormone is increased in experimental intestinal inflammation in rats

Background/Aims - Corticotropin releasing hormone (CRH) suppresses immunological functions via stimulation of the pituitary-adrenal axis, but is also found in peripheral tissues. Peripheral proinflammatory activity of CRH is suggested by increased tissue concentrations in arthritis and in vitro immunostimulatory effects. This study evaluated intestinal CRH concentrations, immunolocalisation, and synthesis in chronic enterocolitis and investigated in vitro responsiveness of lamina propria mononuclear cells to CRH. Methods - Chronic granulomatous enterocolitis was induced by intramural injection of peptidoglycan-polysaccharide polymers in the ileocaecal region of Lewis rats. CRH protein was measured in caecal specimens by immunohistochemistry and radioimmunoassay and caecal CRH mRNA expression was analysed by reverse transcriptase polymerase chain reaction. Results - In the chronically inflamed caecum abundant immunoreactive CRH was found in inflammatory cells, mesenchymal cells, as well as in myenteric plexi. In contrast, only a few CRH containing cells were detected in normal and HSA injected control caecums. Moreover, caecal CRH protein levels were increased during chronic enterocolitis. Local CRH synthesis as indicated by mRNA expression was considerably increased in chronic enterocolitis whereas it was undetectable or low in uninflamed caecum. In addition, CRH stimulated in vitro proliferation of lamina propria mononuclear cells and inhibited mitogen induced proliferation. Conclusion - Increased CRH protein and mRNA expression in chronic enterocolitis and responsiveness of intestinal mononuclear cells to CRH indicate an immunomodulatory role for locally produced CRH in intestinal inflammation.