SICKNESS BEHAVIOR IN MICE DEFICIENT IN INTERLEUKIN-6 DURING TURPENTINE ABSCESS AND INFLUENZA PNEUMONITIS

Interleukin-6 (IL-6), among other cytokines, is thought to be involved in the regulation of sickness behavior (e.g., anorexia, cachexia, fev er, and lethargy) induced by infections (bacterial and viral origin) a nd sterile tissue necrosis (burns and surgical traumas). Mice deficien t in IL-6 (IL-6 KO) were generated by gene targeting. Homozygous IL-6 KO male and female mice and their appropriate controls were implanted with biotelemeters to monitor body temperature (T-b) and motor activit y (Act). Normal circadian rhythms in T-b and Act as well as rates of f ood intake and weight gain did not differ significantly between sex-ma tched IL-6 KO and control groups at 30 degrees C in a 12:12-h light-da rk cycle. Sterile tissue damage was induced in mice by subcutaneous in jection of turpentine (0.1 mi, left hindlimb). Influenza pneumonitis w as induced by intranasal inoculation of mouse-adapted influenza A viru s (17.5 plaque-forming units). Lack of IL-6 completely prevented fever , anorexia, and cachexia because of turpentine abscess in both sexes. It did not prevent lethargy, although IL-6 KO mice recovered to normal Act significantly sooner than wild-type mice. Symptoms of sickness we re only slightly modified during influenza virus infection in IL-6 KO mice. Attenuation of sickness behavior was more pronounced in IL-6 KO female than in male mice. We conclude that, although IL-6 is induced d uring both turpentine abscess and influenza infection, this cytokine a ppears to be more critical in induction of the symptoms of sickness be havior during sterile tissue abscess than during influenza infection.