Increased tumor necrosis factor-alpha production by peripheral blood leukocytes from TCDD-exposed rhesus monkeys

Previous work has shown that exposure to 2,3,7,8-tetrachrorodibenzo-p-dioxi n (TCDD) is associated with a dose-dependent increase in the incidence and severity of endometriosis in the rhesus monkey, Studies also suggest that i mmune mechanisms participate in TCDD-mediated toxicity and the pathogenesis of endometriosis, Thirteen years after TCDD treatment was terminated, we c haracterized the phenotypic distribution of peripheral blood mononuclear ce lls (PBMC) from TCDD-exposed and -unexposed rhesus monkeys and determined t he ability of these cells to produce cytokines and exert cytolytic activity against NK and T-cell-sensitive cell lines. We also determined whether ele vated serum levels of TCDD, dioxin-like PHAH congeners, and triglycerides c orrelated with changes in PBMC phenotype or function. For all animals, TCDD exposure correlated with increased PBMC tumor necrosis factor-alpha (TNF-a lpha) secretion in response to stimulation by T-cell mitogen and decreased cytolytic activity against NK-sensitive target cells. Furthermore, increase d production of this cytokine by PHA-stimulated leukocytes was associated w ith elevated serum triglyceride levels. Leukocyte TNF-alpha secretion in re sponse to viral antigen and PBMC production of interferon gamma (IFN gamma) , IL-6, and IL-10 following exposure to mitogen or antigen were unaffected by previous TCDD treatment. Although TCDD exposure was not associated with changes in PBMC surface antigen expression, elevated serum concentrations o f TCDD, 1,2,3,6,7,8-hexachlorodibenzofuran and 3,3',4,4',5-pentachlorobiphe nyl correlated with increased numbers of CD3+/ CD25- and CD3-/CD25f leukocy tes and enhanced secretion of TNF-alpha by mitogen-stimulated PBMC. These f indings indicate that TCDD-exposed rhesus monkeys with endometriosis exhibi t long-term alterations in systemic immunity associated with elevated serum levels of specific PHAH congeners.