Studies on the immunosuppressive properties of 7,25-dihydroxycholesterol--I. Reduction of interleukin production by treated lymphocytes.
Several oxysterols are powerful immunosuppressors. Among them 7,25-dihydroxycholesterol (7,25-OHC) seems to be particularly interesting. The effect of this synthetic sterol on murine lymphocytes, stimulated by Con A, or by allogeneic or TNP-modified syngeneic lymphocytes, was investigated. The results showed that the induction of cytotoxic T-lymphocytes (CTL) was strongly inhibited by a treatment with non-toxic concentrations of this sterol. A marked reduction of interleukin 2 (IL-2) production by alloantigen stimulated lymphocytes occurred at the same concentrations. We also showed that receptors to IL-2 did not appear on lymphocytes stimulated by Con A, when 7,25-OHC was added at the beginning of the culture. The addition of exogenous IL-2 to the culture was found to only slightly reverse the inhibition caused by 7,25-OHC. Taken together, these results indicate that an impairment at the early steps of lymphocyte activation, involving IL-2 secretion, could be responsible, at least in part for the various immunosuppressive effects of 7,25-OHC.
Moog
C
C
Laboratoire de Chimie Organique des Substances Naturelles, UA 31, CNRS, Strasbourg, France.
Luu
B
B
Beck
J P
JP
Italiano
L
L
Bischoff
P
P
D000818:Animals; D005260:Female; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007166:Immunosuppressive Agents; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
D006888:Hydroxycholesterols; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; C057657:7,25-dihydroxycholesterol