Behavioral effects of infection with IL-6 adenovector

The onset of autoimmunity in lupus-prone mice is accompanied by a constella tion of behavioral deficits, termed Autoimmunity-Associated Behavioral Synd rome (AABS). In particular, a spontaneous increase in serum interleukin-6 ( IL-6) levels in five-week old MRL-lpr mice coincides temporally with blunte d responsiveness to sucrose and excessive immobility in the forced swim tes t. These relationships, along with evidence that sucrose intake drops after systemic IL-6 overexpression is induced in healthy mice, have led to the h ypothesis that sustained elevation in serum IL-6 also induces other aspects of AABS. This hypothesis is tested by comparing the behavioral profiles of healthy mice infected with Ad51mIL6 adenovirus (2 x 10(8) pfu of virus/mou se i.p.) with those of animals infected with control Ad5 virus. This method ology was used to achieve high circulating levels of IL-6, to overcome the problem of its short half-life, and to avoid the stressful effects of repea ted injections. The Ad5mIL6 infection (known to induce excessive IL-6 level s over five days) transiently reduced food, water, and sucrose intake, as w ell as rectal temperature in MRL +/+ and AKR/J mice. Although the level of locomotor activity did not decline, Ad5mIL6-infected AKR/J mice demonstrate d less novel object exploration. Performance in the step-down, plus-maze, a nd spontaneous alternation tests were disturbed to various degrees in all i nfected animals. The present results suggest that prolonged exposure to cir culating IL-6 primarily impairs ingestive behavior, likely reflecting enhan ced catabolism. The inability of circulating IL-6 to alter other aspects of behavior supports the hypothesis that multiple immuno-neuroendocrine mecha nisms contribute to the pathogenesis of AABS. (C) 2001 Academic Press.