Dyslipidemia can reduce the immunosuppressive effects of cyclosporine.
OBJECTIVE
Dyslipidemia is a significant risk factor for the development of atherosclerotic disease and of chronic allograft rejection. Few data are available on the effects of dyslipidemia on the immunosuppressive action of immunosuppressive agents. We investigate the in vitro effects of lipids solution on the immunosuppressive action of cyclosporine (CsA).


METHODS
Peripheral blood mononuclear cells (PBMC) were PHA or OKT3 activated in vitro with/without different concentrations of Intralipid solution (INT, range 0.5% to 15%). CsA inhibition of activation was measured after a 3 day incubation, by adding H3-thimidine. The intracellular concentration of CsA was measured by radioimmunoassay and related to the CsA inhibitory effects.


RESULTS
Increasing INT concentration in the medium, CsA inhibition of PBMC activation by PHA or OKT3 was reduced from 72+/-13% to 8+/-2% and from 80+/-10% to 18+/-3%, respectively. A significant reduction of the intracellular CsA concentration was also evident with increasing INT concentrations and was related to the inhibitory activity of CsA.


CONCLUSIONS
These results suggest that dyslipidemia may reduce the availability of intracellular CsA concentration to inhibit the immune activation process and may explain the relationship between dyslipidemia and chronic allograft loss.
D002478:Cells, Cultured; D016572:Cyclosporine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D050171:Dyslipidemias / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology
D007166:Immunosuppressive Agents; D016572:Cyclosporine