Prostaglandin E-2 inhibits lesion formation in dextran sodium sulphate-induced colitis in rats and reduces the levels of mucosal inflammatory cytokines

Effects of rectally injected prostaglandin E-2 (PGE(2)) in rats with dextra n sodium sulphate (DSS)-induced colitis were investigated in terms of histo pathology, local myeloperoxidase (MPO) activity, local mRNA expression of i nterleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha) and growth-regulated gene produced/cytokine-induced neutrophil chemoattractant (GRO/CINC)-1, and secretion of TNF-alpha and GRO/CINC-1. In animals with n o PGE(2) treatment, DSS-induced erosion and ulceration were particularly se vere in the rectum and extended to the proximal colon. Neutrophil infiltrat ion was characteristically present in the lesions and surrounding mucosa. M PO activity at lesion sites was increased. IL-1 beta and GRO/CINC-1 mRNA ex pression was increased, while TNF-alpha mRNA expression was significantly d ecreased. GRO/CINC-1 secretion was increased but a similar elevation of TNF -alpha was not detected. In the PGE(2)-treated group, lesion formation was inhibited grossly and microscopically. Neutrophil infiltration and MPO acti vity in and around lesions were lessened. The reduction in TNF-alpha mRNA e xpression and secretion was not affected by PGE(2). The expression of mRNA for IL-1 beta and GRO/CINC-1 was reduced, as was the secretion of GRO/CINC- 1. As mRNA expression and secretion of cytokines in lesions of non-PGE(2)-t reated animals was similar to that reported in human ulcerative colitis, re ctal injection of PGE(2) may prove to be an effective therapy.