Effects of raloxifene, a selective estrogen receptor modulator, on thymus,T cell reactivity, and inflammation in mice

Raloxifene is a selective estrogen receptor modulator approved for preventi on of osteoporosis in postmenopausal women. It is selective by virtue of ha ving estrogen agonistic effects in bone, vessels, and blood lipids, while i t is antagonistic with mammary and uterine tissue. The aim of the study was to examine whether the raloxifene analogue LY117018 (LY) has estrogenic ef fects on the thymus, T cell responsiveness, and inflammation. Oophorectomiz ed normal mice were treated with subcutaneous injections of equipotent anti osteoporotic doses of LY (3 mg/kg) and 17 beta -estradiol (E2) (0.1 mg/kg) or vehicle as controls, Effects on thymus were studied by analyses of thymu s weight, cellularity, and CD4 and CD8 phenotype expression and histology, while inflammation was determined as T-cell-mediated delayed-type hypersens itivity (DTH) and granulocyte-mediated footpad swelling. LY lacked the supp ressive properties of E2 on DTH and granulocyte-mediated inflammation. Furt hermore, LY induced only minor thymus atrophy compared with E2 and did not, in contrast to E2, alter the thymic CD4/CD8 phenotypes. These results clea rly demonstrate that raloxifene principally lacks the modulatory effects of estrogen on T cell responsiveness and inflammation. Our data are discussed in the context of recent findings in estrogen receptor biology and also wi th respect to estrogen-mediated alteration of autoimmune rheumatic diseases , (C) 2000 Academic Press.