Behavioral effects of infection with IL-6 adenovector.
The onset of autoimmunity in lupus-prone mice is accompanied by a constellation of behavioral deficits, termed Autoimmunity-Associated Behavioral Syndrome (AABS). In particular, a spontaneous increase in serum interleukin-6 (IL-6) levels in five-week old MRL-lpr mice coincides temporally with blunted responsiveness to sucrose and excessive immobility in the forced swim test. These relationships, along with evidence that sucrose intake drops after systemic IL-6 overexpression is induced in healthy mice, have led to the hypothesis 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 Ad5mIL6 adenovirus (2 x 10(8) pfu of virus/mouse i.p.) with those of animals infected with control Ad5 virus. This methodology 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 repeated injections. The Ad5mIL6 infection (known to induce excessive IL-6 levels over five days) transiently reduced food, water, and sucrose intake, as well as rectal temperature in MRL +/+ and AKR/J mice. Although the level of locomotor activity did not decline, Ad5mIL6-infected AKR/J mice demonstrated less novel object exploration. Performance in the step-down, plus-maze, and spontaneous alternation tests were disturbed to various degrees in all infected animals. The present results suggest that prolonged exposure to circulating IL-6 primarily impairs ingestive behavior, likely reflecting enhanced catabolism. The inability of circulating IL-6 to alter other aspects of behavior supports the hypothesis that multiple immuno-neuroendocrine mechanisms contribute to the pathogenesis of AABS.
Sakić
B
B
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Gauldie
J
J
Denburg
J A
JA
Szechtman
H
H
D000256:Adenoviridae / Q000235:genetics*; D000257:Adenoviridae Infections / Q000276:immunology; D000818:Animals; D000855:Anorexia / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D001522:Behavior, Animal / Q000502:physiology*; D001831:Body Temperature; D003213:Conditioning, Psychological / Q000502:physiology; D004326:Drinking / Q000276:immunology; D004644:Emotions / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology; D005822:Genetic Vectors; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D019463:Mice, Inbred MRL lpr; D015213:Neuroimmunomodulation / Q000502:physiology; D013395:Sucrose
D015850:Interleukin-6; D013395:Sucrose