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 Res. 11:39). The aim of the present work was to investigate the mechanism(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 TNF release. Previous work has shown that PS induces histamine release by mast cells and it is known that histamine inhibits TNF release. PS treatment of W/WV mice lacking mast cells, which are therefore unable to 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 LPS-induced TNF release, while the effect of PS was evident in sham-operated mice. PS treatment in adrenalectomized mice was associated with an increase in TNF serum levels when compared to untreated animals. Overall these results suggest that PS inhibition of LPS-induced TNF release is dependent on adrenal hormones, while PS, in the absence of adrenal hormones, seems to have a priming effect on the cells that produce TNF after LPS stimulus.