Effect of Misoprostol on Acute and Chronic Inflammation.
Prostaglandins and their fatty acid precursors are important to regulation of cell function, and immune and inflammatory responses. Prostaglandin E compounds in particular have been shown to reduce inflammation and tissue injury. We examined the ability of misoprostol, the orally active analog of Prostaglandin E1, to influence inflammation in two animal models. In the subcutaneous air pouch model, acute inflammation was induced by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). Misoprostol reduced pouch leukocyte counts in a dose dependent manner (33--49% v control), but did not alter fluid accumulation. The non-steroidal antiinflammatory agent, diclofenac, also reduced leukocyte counts in a dose dependent manner (28--66%) without affecting pouch fluid volume. Low dose misoprostol and low dose diclofenac used together reduced leukocyte counts by 39%, suggesting an advantageous snyergy in suppression of acute inflammation. Collagen induced arthritis (CIA) is a model of chronic inflammation. Misoprostol had no effect on the severity or course of CIA. Diclofenac reduced significantly all indices of inflammation tested, including joint swelling, number of affected joints and ability to walk. Misoprostol interfered with the antiinflammatory effect of diclofenac when the two compounds were administered together in the CIA model. These studies suggest that Misoprostol suppresses neutrophil mediated acute inflammation.
Rossetti
Ronald G.
RG
Seiler
Christina M.
CM
Brathwaite
Kevin
K
Zurier
Robert B.
RB