Human natural tumor necrosis factor alpha induces multiple endocrine and hematologic disorders in rats

Slc:Wistar male rats treated with human natural tumor necrosis factor or (h n TNF-alpha, 3 x 10(5) Japan reference units/kg intravenously) for 3 months showed histologic vacuolation of basophils in the anterior pituitary, hype rplasia of the thyroidal Follicular epithelium, and hyperplasia of the test icular interstitial cells. The vacuolated basophils were immunohistochemica lly shown to be thyrotrophs. In addition, there were decreases in plasma le vels of triiodothyronine (T3), thyroxin (T4), and testosterone, and an incr ease in thyroid-stimulating hormone (TSH). The number of lymphocytes in the marginal zones of lymphoid follicles in spleen and lymph nodes and B-lymph ocytes in the peripheral blood decreased. Hyperplasia of hematopoietic cell s in the bone marrow and decreases in both leukocytes and erythrocytes in t he peripheral blood were prominent. Hyperplasia of bile ductular epithelial cells with periportal mononuclear cell infiltration in the Liver and incre ased cellularity in alveolar walls in the lung were also characteristic. In in vitro studies, hn TNF-alpha inhibited both proliferation and peroxidase activity of thyroid follicular epithelial cells. These findings demonstrat e that hn TNF-alpha may induce histologic vacuolation of thyrotrophs by cau sing a decrease in plasma levels of T3 and T4: hyperplasia of the thyroid f ollicular epithelium, which may be attributed to the increased plasma level of TSH; hyperplasia of testicular interstitial cells, by lowering the plas ma level of testosterone; hyperplasia of bile ductular epithelial cells; hy perplasia of hematopoietic cells in bone marrow; and the increase in cellul arity in pulmonary alveolar walls. In addition, hn TNF-alpha may suppress t he differentiation of B-lymphocytes.