Exposure to ultraviolet radiation enhances mortality and pathology associated with influenza virus infection in mice

Ultraviolet radiation (UVR) causes systemic immune suppression, decreasing the delayed type and contact hypersensitivity responses in animals and huma ns and enhancing certain mycobacterial, parasitic and viral infections in m ice. This study tests the hypothesis that prior exposure to UVR enhances in fluenza infections in mice. BALB/c female mice were exposed to 0-8.2 kJ/m(2 ) of UVR, Exposed and unexposed mice were infected intranasally three days later with 150-300 plaque-forming units/mouse (lethal dose (LD)(20)-LD40) o f mouse-adapted Hong Kong Influenza A/68 (H2N2) virus or sham infected with 50 muL Hanks' balanced salt solution/mouse. Mortality from viral infection ranged from 25-50%, UVR exposure increased virus-associated mortality in a dose-dependent manner (up to a two-fold increase at 8.2 kJ/m(2)). The incr eased mortality was not associated with bacterial pneumonia, The highest do se of UVR also accelerated the body weight loss and increased the severity and incidence of thymic atrophy associated with influenza infection, Howeve r, UVR treatment had little effect on the increase in lung wet weight seen with viral infection, and, to our surprise, did not cause an increase in vi rus titers in the lung or dissemination of virus. The mice died 5-6 days af ter infection, too early for adaptive immune responses to have much impact. Also, UVR did not interfere with the development of protective immunity to influenza, as measured by reinfection with a lethal challenge of virus. Al so, cells adoptively transferred from UVR or untreated mice were equally pr otective of recipient mice challenged with a lethal dose of virus. The mice resemble mice succumbing to endotoxin, and influenza infection increased t he levels of tumor necrosis factor or (TNF-alpha) in bronchoalveolar lavage fluid and serum cortisol levels; however, UVR preexposure did not increase either of these responses to the virus. The results show that UVR increase d the morbidity, mortality and pathogenesis of influenza virus in mice with out affecting protective immunity to the virus, as measured by resistance t o reinfection. The mechanism of enhanced mortality is uncertain, but the da ta raises concerns that UVR may exacerbate early responses that contribute to the pathogenesis of a primary viral infection.