Abstract
The immunosuppressive effects of 2ยท5 (n = 6) and 5 mg kg^โ1^ day^โ1^ (n = 7) of cyclosporine (CSA) given intravenously for 9 days to the immunized, hyperlipidemic Zucker rat model were compared with drugโfree animals (n = 6) and lean litterโmates given 0 (n = 6), 5 (n = 6), and 10 mg kg^โ1^ day^โ1^ (n = 8) of CSA. Thus, based on body weights, both obese rats and lean litterโmates 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 litterโmates. CSA concentrations in whole blood, serum, and the lipoprotein fractions obtained 4h after the final dose were greater in obese rats compared with lean litterโmates. Immunosuppressive activity, as assessed by ex vivo Tโlymphocyte 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 = 0ยท95, p ยฑ 0ยท0001), 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.