The Prostaglandin Analogs, Misoprostol and SC-46275, Potently Inhibit Cytokine Release from Activated Human Monocytes

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Abstract
Inflammatory mediator release is one of the body's responses to tissue injury and inflammation. These mediators, such as interleukin-1B (Il-1B), tumor necrosis factor (TNF-α), and products of arachidonic acid metabolism, are themselves proinflammatory. Purified human monocytes stimulated in vitro with E. coli-derived lipopolysaccharide (LPS) will release these key cytokines along with various other eicosanoid mediators. Monocytes incubated with LPS and the prostaglandin E-l analog, misoprostol, released significantly lower levels of cytokines compared to monocytes incubated with LPS alone. Eicosanoid release was also affected by misoprostol. SC-46275, a more potent mucosal protective PGEj analog, also altered the release of cytokines and eicosanoids from human monocytes. However SC-46275 inhibited Il-1B release with an IC50 value of 9 μM compared to 75 μM for misoprostol. SC-46275 and misoprostol both inhibited TNF-α release. These data suggest there is a potential immunomodulatory role for prostaglandin analogs in the therapeutic treatment of inflammatory diseases such as ulcerative colitis, Crohn's disease, and autoimmune inflammatory diseases of the central nervous system.