Ef. Secchi et al., ADRENALECTOMY ABOLISHES PHOSPHATIDYLSERINE INHIBITION OF LIPOPOLYSACCHARIDE-INDUCED TUMOR-NECROSIS-FACTOR RELEASE, European cytokine network, 4(5), 1993, pp. 371-375
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.