Prostaglandin E2 enhances interleukin 8 (IL-8) and IL-6 but inhibits GMCSF production by IL-1 stimulated human synovial fibroblasts in vitro.

OBJECTIVE: To examine in vitro the effect of prostaglandin E2 (PGE2) on synovial cell cytokine production. METHODS: Human synovial fibroblasts were stimulated with PGE2 alone or PGE2 in combination with interleukin 1 alpha (IL-1 alpha) (5 ng/ml) and/or indomethacin (10(6) M) and assessed for the production of IL-8, IL-6, and granulocyte macrophage colony stimulating factor (GMCSF) at the protein and messenger RNA (mRNA) levels. RESULTS: PGE2 alone had little detectable effect on IL-8 or GMCSF; however, a small enhancement of both IL-6 mRNA and protein levels was seen. While all cytokines were markedly stimulated by IL-1 alpha), co-addition of the cyclooxygenase inhibitor indomethacin enhanced IL-8 and GMCSF levels, but caused a reduction in IL-6 expression. The addition of PGE2 to cultures stimulated with IL-1 alpha and indomethacin resulted increases in IL-6 mRNA and protein expression while causing a concomitant reduction in GMCSF protein and mRNA expression. PGE2 and illoprost (PGI2 analog) enhanced IL-8 production in stimulated cells. CONCLUSION: While PGE2 alone has limited effects on synovial cell production of IL-8 and GMCSF, its effects are significant in context of IL-1 alpha stimulation; endogenous PGE2 may alter cytokines secreted by mesenchymally derived cells. PGE2 may be an important modulator of cytokine driven inflammation.