ADHESION-INDEPENDENT SYNERGY OF MONOCYTES AND ENDOTHELIAL-CELLS IN CYTOKINE PRODUCTION - REGULATION OF IL-6 AND GM-CSF PRODUCTION BY PAF

Co-cultures of monocytes (MO) and endothelial cells (EC) were studied for their capacity to synergize in the production of interleukin-6 (IL -6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), two cytokines potentially important in vascular physiopathology. Resting monocytes produced detectable amounts of IL-6 but no GM-CSF, whereas c onfluent EC produced significant quantities of GM-CSF, but minimal IL- 6, In cocultures without stimuli, additive synthesis of both cytokines was observed. When EC were pretreated however, with either PAF, TNF o r both stimuli, before addition of MO, synergistic production of IL-6 was observed In contrast GM-CSF production was not enhanced by cocultu re of monocytes with activated EC. When either cell population was fix ed with paraformaldehyde or killed by freeze-thawing before addition t o the co-culture, cytokine levels reverted to those produced by the un affected population alone. On the other hand, separating the two cell populations by a cell-impermeable membrane in transwell cultures did n ot affect the synergistic production of the cytokines. Taken together, our data suggest that EC and MO can synergize in response to stimuli by producing IL-6 and that this synergy is dependent on the integrity of both cell populations, but independent of cell-cell contact.