Immunosuppressive effect of cyclosporine in the hyperlipidemic rat model

The immunosuppressive effects of 2.5 (n = 6) and 5 mg kg-1 day-1 (n = 7) of cyclosporine (CSA) given intravenously for 9 days to the immunized, hyperlipidemic Zucker rat model were compared with drug-free animals (n = 6) and lean litter-mates given 0 (n = 6), 5 (n = 6), and 10 mg kg-1 day-1 (n = 8) of CSA. Thus, based on body weights, both obese rats and lean litter-mates received total doses of 0, 1, and 2 mg of CSA. No significant differences in percent change in baseline body weight were found; in contrast, spleen weights were markedly greater in treated animals compared with controls. Serum cholesterol, triglycerides, and lipoprotein levels of obese rats were significantly greater than values found in lean litter-mates. CSA concentrations in whole blood, serum, and the lipoprotein fractions obtained 4 h after the final dose were greater in obese rats compared with lean litter-mates. Immunosuppressive activity, as assessed by ex vivo T-lymphocyte proliferation assay, was equivocal between all rats given CSA, independent of dose and obesity, and significantly greater than control animals. Whereas serum CSA levels were correlated to cholesterol levels (r = 0.95, p < 0.0001), there were no significant correlations with immunosuppressive activity. The present data suggest that increased binding of CSA to lipoproteins in the vascular compartment does not significantly impact on its immunosuppressive activity.