Effects of prostaglandins and cAMP levels on monocyte IL-1 production.
The effects of prostaglandin E2 (PGE2), as well as other cAMP-elevating agents, on the in vitro production of interleukin-1 (IL-1) by human monocytes (HM) were examined. Exposure to E. coli lipopolysacharide (LPS) resulted in a dose- and time-dependent increase of IL-1 activity in monocytes culture supernatants. Maximal levels of secreted IL-1 in response to 10 ng LPS/ml were obtained at 18 h. PGE1, PGE2, cholera toxin (CT) and the phosphodiesterase inhibitor, isobutylmethylxanthin (IBMX), when added with LPS, resulted in a dose-dependent increase in cellular cAMP and in secreted IL-1. Maximal levels of secreted IL-1 were 2.5-5.0-fold over LPS alone. When CT or PGE2 was added with IBMX a further increase was observed. These agents exhibited marginal effect on cell-associated IL-1. Maximum cAMP levels was achieved at 10 min in response to either PGE1 or PGE2 and returned to near basal levels after 18 h. While PGE1 elevated cAMP to a larger extent than PGE2 (58- vs. 30-fold) the latter resulted in a higher levels of secreted IL-1. Elevated cAMP persisted throughout the entire culture period in response to CT (4-6-fold) or IBMX (7-fold). Thus, we conclude that in adherent HM, IL-1 production is potentiated and not inhibited by prostaglandins or agents that elevate cellular cAMP.
Kassis
S
S
Department of Immunology, Smith Kline & French Laboratories, Swedeland, PA 19279.
Lee
J C
JC
Hanna
N
N
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011453:Prostaglandins; D002772:Cholera Toxin; D000242:Cyclic AMP; D000527:Alprostadil; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine