Soluble IL-2 receptor and CD25 cells in psoriasis: effects of cyclosporin A and PUVA therapy.

A study was conducted to quantify soluble IL-2 receptor (sIL-2R) levels in sera of 57 chronic plaque psoriasis patients and correlate these measurements with disease activity and the number of IL-2R-positive (CD25+) lymphocytes in lesional biopsies of 11 cyclosporin A (CsA) and 13 psoralen plus ultraviolet radiation (PUVA) treated patients. Levels of sIL-2R showed a strong correlation with the psoriasis area and severity index (PASI). CsA and PUVA significantly reduced the PASI and sIL-2R levels to a similar degree after 4 weeks of treatment. Although the majority of CsA-treated patients who were biopsied showed reductions in lesional CD25+ cells, these did not reach statistical significance; in five patients biopsied who had PUVA treatment, no consistent effect on the numbers of CD25+ cells was observed. A significant correlation was found between CD25+ cells in lesional biopsies and the PASI score.

Influence of the hepatic drug-metabolizing enzyme-inducer phenobarbitone on cyclosporine nephrotoxicity and hepatotoxicity in renal-allografted rats.

We have investigated the influence of phenobarbitone ([PB]; 40 mg/kg/day), an inducer of hepatic drug metabolism, on high-dose cyclosporine ([CsA] 40 mg/kg/day) nephrotoxicity in normal Lewis (Lew) and renal allografted (DA X Lew F1----Lew) rats of both sexes. In untreated normal animals, CsA nephrotoxicity, assessed biochemically and histologically, in terms of acute and chronic renal structural damage, was consistently greater in male than in female rats. The capacity of PB to induce CsA metabolism was accompanied in normal rats by reductions in nephro- and hepatotoxicity and by prolonged survival of both female and male rats. Similar reductions in CsA-induced renal functional impairment and acute tubular cell injury were achieved in transplanted female (but not male) animals by concomitant PB administration. Continuous PB treatment in transplanted rats was, however, associated with the appearance of hepatic necrosis. While this effect of PB, and its failure to reduce CsA-induced chronic renal damage mitigate against its prospective value in reversing CsA toxicity, PB may nevertheless prove valuable in assessing further the role of drug metabolism in the pathogenesis of CsA nephrotoxicity.