Brevetoxin Inhalation Alters the Pulmonary Response to Influenza A in the Male F344 Rat

• Published in: Journal of Toxicology and Environmental Health, Part A Vol. 74; no. 5; pp. 313 - 324
• Main Authors: Benson, Janet M., Wolf, Molly L., Kajon, Adriana, Tibbetts, Brad M., Bourdelais, Andrea J., Baden, Daniel G., March, Thomas H.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 01.01.2011; Taylor & Francis Ltd
• Subjects: Administration, Intranasal; Aerosols; Algae; Animals; Bronchiolitis, Viral - immunology; Bronchiolitis, Viral - pathology; Bronchiolitis, Viral - virology; Cytokines; Cytokines - metabolism; Delay; Disease Susceptibility; Epidemiology; Harmful Algal Bloom; Immunity, Mucosal - drug effects; Indication; Influenza; Influenza A virus; Influenza A Virus, H3N2 Subtype - growth & development; Influenza A Virus, H3N2 Subtype - immunology; Influenza A Virus, H3N2 Subtype - isolation & purification; Influenza virus; Inhalation; Lung - drug effects; Lung - immunology; Lung - pathology; Lung - virology; Lungs; Male; Males; Marine Toxins - administration & dosage; Marine Toxins - toxicity; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - metabolism; Orthomyxoviridae Infections - pathology; Orthomyxoviridae Infections - virology; Oxocins - administration & dosage; Oxocins - toxicity; Random Allocation; Rats; Rats, Inbred F344; Red tide; Rodents; Time Factors; Toxicology; Toxins; Viral Load; Florida; USA, Florida
• ISSN: 1528-7394; 1087-2620; 2381-3504
• DOI: 10.1080/15287394.2010.519316

Epidemiological studies demonstrated that the number of emergency-room visits for respiratory indications increases during periods of Florida Red Tides. The purpose of this study was to examine whether or not repeated brevetoxin inhalation, as may occur during a Florida Red Tide, affects pulmonary responses to influenza A. Male F344 rats were divided into four groups: (1) sham aerosol/no influenza; (2) sham aerosol/influenza; (3) brevetoxin/no influenza; and (4) brevetoxin/influenza. Animals were exposed by nose-only inhalation to vehicle or 50 μg brevetoxin-3/m 3 , 2 h/d for 12 d. On d 6 of aerosol exposure, groups 2 and 4 were administered 10,000 plaque-forming units of influenza A, strain HKX-31 (H3N2), by intratracheal instillation. Subgroups were euthanized at 2, 4, and 7 d post influenza treatment. Lungs were evaluated for viral load, cytokine content, and histopathologic changes. Influenza virus was cleared from the lungs over the 7-d period; however, there was significantly more virus remaining in the group 4 lungs compared to group 2. Influenza virus significantly increased interleukins-1α and -6 and monocyte chemotactic protein-1 in lung; brevetoxin exposure significantly enhanced the influenza-induced response. At 7 d, the severity of perivascular and peribronchiolar inflammatory cell infiltrates was greatest in group 4. Bronchiolitis persisted, with low incidence and severity, only in group 4 at d 7. These results suggest that repeated inhalation exposure to brevetoxin may delay virus particle clearance and recovery from influenza A infection in the rat lung.