Endothelial cells stimulated by inflammatory cytokines can suppress lymphocyte proliferation via the production of platelet-activating factor acting on monocytes.
PAF may mediate endothelial suppression of lymphocyte proliferation in inflammation; leaves open therapeutic targeting of antagonists in human disease.
Human umbilical vein endothelial cells (EC) can respond to endotoxin or to the inflammatory cytokines tumor necrosis factor (TNF) and interleukin 1 (IL-1) by producing platelet-activating factor (PAF). When EC were preexposed to TNF-alpha (25 U/ml) for 1 h, and then washed, their subsequent coculture with peripheral blood mononuclear cells (PBMC) resulted in suppressed proliferative response of the latter to the mitogen Con A (P less than 0.05). This effect was completely reversed by the concomitant use of the PAF receptor antagonist BN 52021 (0.1 mM). Preexposure of EC to IL-1 beta (0.5 U/ml) induced similar effects, but IL-1 and TNF were not additive. Removal of monocytes from the PBMC population abolished the effects. On the other hand, coculture of monocytes with cytokine-preexposed EC resulted in significant induction of suppressor activity on lymphocyte proliferation. Our data indicate that EC, preexposed to inflammatory cytokines, can modulate lymphocyte functions via the production of PAF and its action on monocytes.
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Lacasse et al. (1991) studied this question.
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