Although production and immunological activity of granulocyte-macrophage colony stimulating factor (GM-CSF) have been implicated in the pathogenesis of various disorders, little has been reported concerning the factors involved in the regulation of GM-CSF release. Therefore, we examined the effect of the stable prostacyclin agonist, cicaprost, on the in vitro production of GM-CSF by peripheral blood mononuclear cells (PBMC) obtained from normal subjects by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). Incubation of PBMC (10 6 cells/ml 1 ) with the bacterial lipopolysaccharide (LPS; 0.1 g/ml) for 24 h caused a more than 10-fold concentration-dependent increase of GM-CSF release (401Β±58 pg/mlΓ10 6 cells -1 ). Addition of cicaprost (0,01 ng/ml to 1 g/ml) resulted in a concentration-and time-dependent reduction of LPS-induced GM-CSF secretion by PBMC with a mean IC 50 of 6.7 ng/ml (n=9). Furthermore, cicaprost also inhibited the LPS-elicited expression of GM-CSF mRNA, as determined by RT-PCR. These results demonstrate that prostacyclin inhibits LPS-induced GM-CSF release and that its effects are related to the level of transcription. Hence, our data suggest that cicaprost or related PGI 2 agonists may represent immunomodulators of mononuclear cell function and may offer a therapeutic approach to GM-CSF-mediated inflammatory disorders.