Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Pulmonary Influenza Virus Titer and Natural Killer (NK) Activity in Rats

Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Pulmonary Influenza Virus Titer and Natural Killer (NK) Activity in Rats. Yang, Y. G., Lebrec, H., and Burleson, G. R. (1994). Fundam. Appl. Toxicol. 23, 125-131. Suppression of immune function and enhanced susceptibility to infection in mice is one of the more sensitive indicators of TCDD toxicity. Recent efforts to demonstrate similar effects in the rat have shown that there are considerable differences between the two species. The purpose of this study was to determine the effect of TCDD exposure on (a) an influenza virus host resistance model in rats and (b) natural killer cell activity in the lung and spleen. Fischer 344 rats were treated with 10 μg TCDD/kg body weight via gavage and infected intranasally with rat-adapted influenza virus (RAIV) 7 days later. Virus-augmented NK activity assessed at 48 hr postinfection in the lung was significantly suppressed in rats treated with 3, 10, or 30 μg TCDD/kg body weight. Spontaneous NK activity in either lung or spleen was not affected by TCDD exposure. Significantly higher virus titers were observed on Days 2, 3, and 4 postinfection in the lungs of rats treated with TCDD (10 μg/kg). TCDD had no effect on the amount of virus recovered from nasal lavage. Acute exposure to TCDD did not significantly affect lung and body weights in rats infected with RAIV except in the highest dose (30 μg/kg) treated rats. Rats exposed to repeated doses of TCDD showed a significant increase of lung weights and L/B ratios when rats were infected with RAIV after TCDD exposure. Virus-augmented pulmonary NK activity in these rats was significantly suppressed; however, the suppression was not more profound than that in rats exposed to a single dose of TCDD. However, an increase of lung weights and lung/body weight ratios was observed in RAIV infected rats which were exposed to repeated doses of TCDD (cumulative dose of 10 μ/kg). Virus-augmented NK activity was significantly suppressed in rats exposed to repeated doses of TCDD. Our results showed that TCDD suppressed virus-augmented pulmonary NK activity and this effect may at least in part be related to enhanced susceptibility of rats to influenza virus.