Impaired Recovery from Influenza A/X-31(H3N2) Infection in Mice with 8-Lipoxygenase Deficiency

Lipoxygenase-derived lipid mediators can modulate inflammation and are stimulated in response to influenza infections. We report an effect of 8-lipoxygenase (ALOX8) on the recovery of mice after infection with Influenza virus X31. We compared the responses of 3- and 6-month-old mice with a deletion of ALOX8 (ALOX8(−/−)) to influenza infections with those of age-matched littermate wild-type mice (ALOX8(+/+)). The duration of illness was similar in 3-month-old ALOX8(−/−) and ALOX8(+/+) mice. However, the 6-month-old ALOX8(−/−) mice showed a prolonged state of illness compared with ALOX8(+/+) mice, as evidenced by reduced body temperatures, reduced locomotor activities, and delayed weight recovery. Although residual viral RNA in the lungs at day 10 post-inoculation was significantly influenced by the age of the ALOX8(−/−) mice, there were no significant differences between ALOX8(−/−) and ALOX8(+/+) mice within the same age groups. The levels of cytokines interleukin 6 (IL-6) and keratinocyte chemoattractant (KC) differed significantly between 6-month-old ALOX8(−/−) and ALOX8(+/+) mice 10 days after viral inoculation. Our data suggest that ALOX8 deficiency in mice leads to impaired recovery from influenza infection in an age-dependent manner.