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© 1996 Oxford University Press

research-article

Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Influenza Virus Host Resistance in Mice1

GARY R. BURLESON*,2, HERVÈ LEBREC*,3, YUNG G. YANG*,{dagger},4, JOELLE D. IBANES*,{ddagger},5, KEVIN N. PENNINGTON§,6 and LINDA S. BIRNBAUM*

*U.S. Environmental Protection Agency, Health Effects Research Laboratory Research Triangle Park, North Carolina {dagger}Curriculum in Toxicology, University of North Carolina at Chapel Hill North Carolina {ddagger}Center for Environmental Medicine, University of North Carolina at Chapel Hill North Carolina §ManTech Environmental Research Triangle Park, North Carolina

Received March 1, 1994; accepted July 27, 1995

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes numerous immunotoxic effects including thymic involution and an immunosuppression of nonspecific as well as specific cell- and humoralmediated immunity. TCDD administration to laboratory animals also results in a decreased resistance to numerous bacteria, viruses, and parasites. Effects on virus host resistance appear to be among the most sensitive effects of TCDD immunotoxicity. However, previous studies have not achieved a no effect level. The present studies utilized an influenza virus host resistance model in mice to quantify the sensitivity of this model to TCDD and to determine the NOAEL (no observed adverse effect level) of TCDD for influenza virus. Results indicated that a single dose of TCDD at 0.10, 0.05, or 0.01 µg/kg resulted in an increased mortality to Hong Kong influenza virus when mice were challenged 7 days after TCDD administration. Increased mortality was not correlated with increased virus titers in the lungs. TCDD at 0.005 or 0.001 µg/kg had no effect on influenza-induced mortality. TCDD alone did not affect thymus weight at any dose administered in this study. TCDD also did not alter the virus-enhanced increase in lung weight:body weight ratio nor the virus-induced decrease in thymus weight. Thus, low levels of TCDD exposure lead to enhanced mortality to influenza virus; however, the mechanism of this effect remains to be elucidated. Nonetheless, enhanced mortality to influenza virus in mice following a single dose of 10 ng TCDD/kg represents the most sensitive adverse effect yet reported for TCDD.


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