Effect of Platelet-activating Factor onin vitroandin vivoInterleukin-6 Production

[摘要] The aim of the present study was to investigate the possible effectof platelet-activating factor (PAF), by comparison withinterleukin-1β and polyriboinositic/polyribocytidylic (polyI–C) acid, on IL-6 production by L 929 mouse fibroblasts. Atconcentrations above 1 μM PAF, the production of IL-6 by mousefibroblasts was enhanced in a dose dependent fashion. At 5 μMPAF, the peak increase (60.1 ± 19.4 U/ml) was similar tothat induced by 50 μg/ml poly I–C (60.0 ± 35.0U/ml) and higher than the one evoked by 100 U/ml IL-1β(3.8 ± 1.8 U/ml). The increase of 11-6 activity inducedby 5 μM PAF was maximal after a 22 h incubation period with L 929cells. Lyso-PAF (5 μM) also increased IL-6 activity fromfibroblasts to a similar extent compared with 5 μM PAF. Inaddition, the IL-6 activity induced by 5 μM PAF was stillobserved when the specific PAF antagonist, BN 52021 (10 μM), wasadded to the incubation medium of L 929 cells. The result suggeststhat the production of IL-6 by L 929 cells evoked by PAFinvitrois not receptor mediated. Thein vivoeffect of PAF on IL-6 production was also investigated in the rat.Two hours after intravenous injection of PAF (2 to 4 μg/kg),a dramatic increase of IL-6 activity in rat serum was observed, thiseffect being dose dependent. The increase of IL-6 induced by 3μg/kg PAF was not observed when the animals were treated withthe PAF antagonist, BN 52021 (1 to 60 mg/kg0. These resultsdemonstrate that PAF modulates IL-6 production and that theinvivoeffect is receptor mediated.

[学科分类] 生理学与病理学