Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on blood and spleen natural killer (NK) cell activity in the mouse

The immunotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were studied in male A/J mice after a loading dose of 5 micrograms TCDD/kg body wt. followed by 3 weekly maintenance doses of 1.42 micrograms TCDD/kg b.w. administered intraperitoneally. Tissue samples and immune cells were prepared on two occasions, i.e. on days 28 and 120 after the first injection of TCDD. This dose of TCDD evoked classical histological signs of liver damage and lipid accumulation, as well as thymic atrophy. Red (RBC) blood cell counts were significantly lowered in the TCDD group on day 28, but were normal on day 120. White (WBC) blood cell counts were normal in the TCDD group. Natural killer (NK) cell activity increased 3.4-fold (P less than 0.01) and 2.2-fold (P less than 0.01) in the blood and spleen, respectively, after 28 days, and these effects persisted on day 120. The increased NK-cell activity occurred concomitantly with a decreased proliferative response of spleen lymphocytes to the T-cell mitogen concanavalin A after both 28 (65%) and 120 days (58%). The proliferative response of spleen cells to the B-cell mitogen lipopolysaccharide seemed, however, unaffected. We have thus shown for the first time that TCDD induces an increased activity of NK cells that occurs simultaneously in the blood and spleen. This effect may indicate a general compensatory activation of the body's defences brought about by disturbances in the function of other arms of the immune system.