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.