Modulation of cytokine release from mononuclear cells by prostacyclin, IL-4 and IL-13

In a previous study, we reported that cicaprost, a stable prostacyclin anal ogue can inhibit the release of granulocyte-macrophage colony-stimulating f actor (GM-CSF) from activated human peripheral mononuclear blood cells (PBM Cs), Since interleukin (IL-4) and IL-13 have been shown to inhibit the rele ase of cytokines from PBMCs we tested the hypothesis that prostacyclin in c ombination with IL-4 or IL-13 can act synergistically to modulate the relea se of IL-10, generally associated with anti-inflammatory properties, and th e pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha). For t his purpose, PBMCs were isolated over Ficoll, stimulated with lipopolysacch aride (LPS) and incubated in the presence of cicaprost, IL-4 or IL-13, Ther e was a significant reduction in TNF-alpha as well as IL-10 secretion from LPS-stimulated PBMCs following incubation with IL-4 or IL-13, In contrast, cicaprost reduced the secretion of TNF-alpha but led to a slight enhancemen t of IL-10 release from PBMCs, When LPS-activated PBMCs were incubated in t he presence of cicaprost and IL-4 or IL-13 there was a selective, synergist ic inhibition of the TNF-a release which was not observed for IL-10, Thus, our data suggest that prostacyclin can synergize with cytokines to selectiv ely inhibit the release of pro-inflammatory cytokines from PBMCs. (C) 1999 Academic Press.