EFFECT OF PLATELET-ACTIVATING-FACTOR ON IN-VITRO AND IN-VIVO INTERLEUKIN-6 PRODUCTION

THE aim of the present study was to investigate the possible effect of platelet-activating factor (PAF), by com parison with interleukin-1 b eta and polyriboinositic/ polyribocytidylic (poly I-C) acid, on IL-6 p roduction by L 929 mouse fibroblasts. At concentrations above 1 mu M P AF, the production of 11-6 by mouse fibroblasts was enhanced in a dose dependent fashion. At 5 mu M PAF, the peak increase (60.1 +/- 19.4 U/ ml) was similar to that induced by 50 mu g/ml poly I-C (60.0 +/- 35.0 U/ml) and higher than the one evoked by 100 U/ml IL-1 beta (3.8 +/- 1. 8 U/ml). The increase of IL-6 activity induced tay 5 mu M PAF was maxi mal after a 22 h incubation period with L 929 cells. Lyso-PAF (5 mu M) also increased IL-6 activity from fibroblasts to a similar extent com pared with 5 mu M PAF. In addition, the IL-6 activity induced by 5 mu M PAF was still observed when the specific PAF antagonist, BN 52021 (1 0 mu M), was added to the incubation medium of L 929 cells. The result suggests that the production of IL-6 by L 929 cells evoked by PAF in vitro is not receptor mediated. The in vivo effect of PAF on 11-6 prod uction was also investigated in the rat. Two hours after Intravenous i njection of PAF (2 to 4 mu g/kg), a dramatic increase of IL-6 activity in rat serum was observed, this effect being dose dependent. The incr ease of IL-6 induced by 3 mu g/kg PAF was not observed when the animal s were treated with the PAF antagonist, BN 52021(1 to 60 mg/kg). These results demonstrate that PAF modulates IL-6 production and that the i n vivo effect is receptor mediated.