The immunosuppressant steroid cholesterylphosphoserine inhibits tumour necrosis factor-alpha secretion in vitro and in vivo

The synthetic steroid cholesterylphosphoserine (CPHS) inhibited the secreti on of TNF-alpha in lipopolysaccharide-challenged human monocytes, CPHS (5-2 0 mu M) was effective when added together with the endotoxin, or after an i nterval (1-2 h) sufficient to have allowed for initiation of TNF-alpha synt hesis. Consistently, CPHS did not alter TNF-alpha gene transcription. In co ntrast to its action on TNF-alpha, CPHS showed only marginal effects on int erleukin 1 beta secretion. Given intraperitoneally to mice 2h before lipopo lysaccharide CPHS prevented the rise in plasma TNF-alpha (IC50: 5 mg/kg). T he inhibition of TNF-alpha secretion by CPHS may contribute to the immunosu ppressive activity of this steroid. (C) 2000 Academic Press.