Effects of prostaglandins and cAMP levels on monocyte IL-1 production

Abstract

The effects of prostaglandin E₂ (PGE₂), as well as other cAMP-elevating agents, on thein vitro production of interleukin-1 (IL-1) by human monocytes (HM) were examined. Exposure toE. 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 acheived 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.