The immunosuppressant steroid cholesterylphosphoserine inhibits tumour necrosis factor-alpha secretion in vitro and in vivo.
The synthetic steroid cholesterylphosphoserine (CPHS) inhibited the secretion of TNF-alpha in lipopolysaccharide-challenged human monocytes. CPHS (5-20 microM) was effective when added together with the endotoxin, or after an interval (1-2 h) sufficient to have allowed for initiation of TNF-alpha synthesis. Consistently, CPHS did not alter TNF-alpha gene transcription. In contrast to its action on TNF-alpha, CPHS showed only marginal effects on interleukin 1beta secretion. Given intraperitoneally to mice 2 h before lipopolysaccharide CPHS prevented the rise in plasma TNF-alpha (IC(50): 5 mg/kg). The inhibition of TNF-alpha secretion by CPHS may contribute to the immunosuppressive activity of this steroid.
Facci
L
L
Department of Pharmacology, University of Padova, Padova, Italy.
Cusinato
F
F
Negro
A
A
Monastra
G
G
Signorelli
A
A
Bruni
A
A
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010768:Phosphoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C097061:cholesterylphosphorylserine; D010768:Phosphoserine; D002784:Cholesterol