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Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on influenza virus host resistance in mice. 1996

G R Burleson, and H Lebrec, and Y G Yang, and J D Ibanes, and K N Pennington, and L S Birnbaum
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.

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 humoral-mediated 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 microgram/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 micrograms/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.

UI MeSH Term Description Entries
D007113 Immunity, Innate The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS. Immunity, Native,Immunity, Natural,Immunity, Non-Specific,Resistance, Natural,Innate Immune Response,Innate Immunity,Immune Response, Innate,Immune Responses, Innate,Immunity, Non Specific,Innate Immune Responses,Native Immunity,Natural Immunity,Natural Resistance,Non-Specific Immunity
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D009976 Orthomyxoviridae Infections Virus diseases caused by the ORTHOMYXOVIRIDAE. Orthomyxovirus Infections,Infections, Orthomyxoviridae,Infections, Orthomyxovirus,Swine Influenza,Infection, Orthomyxoviridae,Infection, Orthomyxovirus,Influenza, Swine,Orthomyxoviridae Infection,Orthomyxovirus Infection
D009980 Influenza A virus The type species of the genus ALPHAINFLUENZAVIRUS that causes influenza and other diseases in humans and animals. Antigenic variation occurs frequently between strains, allowing classification into subtypes and variants. Transmission is usually by aerosol (human and most non-aquatic hosts) or waterborne (ducks). Infected birds shed the virus in their saliva, nasal secretions, and feces. Alphainfluenzavirus influenzae,Avian Orthomyxovirus Type A,FLUAV,Fowl Plague Virus,Human Influenza A Virus,Influenza Virus Type A,Influenza Viruses Type A,Myxovirus influenzae-A hominis,Myxovirus influenzae-A suis,Myxovirus pestis galli,Orthomyxovirus Type A,Orthomyxovirus Type A, Avian,Orthomyxovirus Type A, Human,Orthomyxovirus Type A, Porcine,Pestis galli Myxovirus,Fowl Plague Viruses,Influenza A viruses,Myxovirus influenzae A hominis,Myxovirus influenzae A suis,Myxovirus, Pestis galli,Myxoviruses, Pestis galli,Pestis galli Myxoviruses,Plague Virus, Fowl,Virus, Fowl Plague
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D004198 Disease Susceptibility A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. Diathesis,Susceptibility, Disease,Diatheses,Disease Susceptibilities,Susceptibilities, Disease
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D000072317 Polychlorinated Dibenzodioxins Dibenzodioxin derivatives that contain multiple chloride atoms bound to the benzene ring structures. TCDD,Tetrachlorodibenzodioxin,2,3,7,8-Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo-p-dioxins,Dibenzo(b,e)(1,4)dioxin, 2,3,7,8-tetrachloro-,PCDD,Polychlorinated Dibenzo-p-dioxins,Polychlorinated Dibenzodioxin,Polychlorodibenzo-4-dioxin,Polychlorodibenzo-p-dioxin,Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo p dioxins,Dibenzo-p-dioxins, Chlorinated,Dibenzo-p-dioxins, Polychlorinated,Dibenzodioxin, Polychlorinated,Dibenzodioxins, Polychlorinated,Polychlorinated Dibenzo p dioxins,Polychlorodibenzo 4 dioxin,Polychlorodibenzo p dioxin,Tetrachlorodibenzo p dioxin

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