Human monocytes exposed to Biostim (RU 41740) alter lymphocyte mitogenesis: mechanisms of action

The immunomodulatory agent RU 41740 (Biostim), which is derived from Klebsiella pneumoniae, may augment mitogenic responses of purified human blood lymphocytes. In non-purified preparations, however, responses may be sharply reduced due to the fact that Biostim induces monocytes to secrete immunosuppressive factors. This investigation has shown that both these biological activities can be exerted by a single, major glucoprotein fraction of Biostim termed F1. The Biostim-induced suppression of mitogen responses was not blocked by antibodies directed against IFN alpha or IFN gamma, thus speaking against IFN as being a mediator of suppression. Reduced suppression, however, was observed in the presence of drugs which inhibit arachidonic acid transformation. The cyclo-oxygenase inhibitors meclofenamic acid and indomethacin, which diminish biosynthesis of prostaglandins, could partially block the Biostim-induced suppression. Such an effect was not observed with 5,8,11-eicosatrynoic acid (ETI) which is an inhibitor of 12-lipoxygenase and leukotriene biosynthesis. Combinations of ETI and meclofenamic acid, however, were more potent than the latter tested separately. Another drug termed diclofenac Na, which apart from being an inhibitor of cyclo-oxygenase, rapidly clears cells of free arachidonic acid by binding to triglycerides, was found to be the most potent in preventing Biostim-induced suppression of mitogen responses. It is concluded that Biostim-exposed monocytes liberate increased amounts of immunosuppressive eicosanoids such as prostaglandins.