ADRENALECTOMY ABOLISHES PHOSPHATIDYLSERINE INHIBITION OF LIPOPOLYSACCHARIDE-INDUCED TUMOR-NECROSIS-FACTOR RELEASE

The treatment with phosphatidylserine (PS) has recently been shown to inhibit in vivo the lipopolysaccharide (LPS)-induced release of tumor necrosis factor (TNF) (Monastra and Bruni, 1992, Lymphokine Cytokine R es. 11: 39). The aim of the present work was to investigate the mechan ism(s) involved in the inhibition by PS. No in vitro inhibition of LPS -induced TNF release was observed when PS was used in vitro with human whole blood cells. The opposite was observed, in vitro PS enhanced TN F release. Previous work has shown that PS induces histamine release b y mast cells and it is known that histamine inhibits TNF release. PS t reatment of W/WV mice lacking mast cells, which are therefore unable t o release histamine, resulted in inhibition of LPS-induced TNF release ; thus excluding a major role of histamine in mediating PS inhibition. However, in adrenalectomized mice PS treatment failed to inhibit the UPS-induced TNF release, white the effect of PS was evident in sham-op erated mice. PS treatment in adrenalectomized mice was associated with an increase in TNF serum levels when compared to untreated animals. O verall these results suggest that PS inhibition of LPS-induced TNF rel ease is dependent on adrenal hormones, while PS, in the absence of adr enal hormones, seems to have a priming effect on the cells that produc e TNF after LPS stimulus.