Cyclic adenosine monophosphate decreases the secretion, but not the cell-associated levels, of interleukin-1 beta in lipopolysaccharide-activated human monocytes

Abstract

Interleukin-1 beta (IL-1 beta) is a cytokine produced mainly by activated monocytes though the mechanism by which it is released is still unknown. Elevation of intracellular cyclic adenosine monophosphate (cAMP) is considered an important down-regulative signal in the production of IL-1 beta in lipopolysaccharide (LPS)-induced monocytes. In this study we show that in LPS-activated human monocytes, elevated cAMP concentrations (induced by either prostaglandin E2, forskolin or dibutyrylcyclic AMP) affected specifically secretion of IL-1 beta; the amount of secreted IL-1 beta was clearly reduced whereas the cell-associated level remained unchanged. TNF-alpha, a normal secretory protein, was used as a control. Cyclic AMP also inhibited TNF production by monocytes, but the decrease was of the same magnitude in the extracellular and intracellular compartments. Thus, the down-regulative effect of cAMP on the production of these monokines is clearly different.