ИСТИНА

Systemic inflammation accompanies the majority of diseases and has a substantial influence on behavior and metabolism. Key proinflammatory cytokines, IL-1, TNF, and IL-6, are involved in inflammation-induced fatigue, however, the exact mechanisms of their action are not completely studied. We addressed the impact of IL-6 on behavior and physical performance during acute inflammation. We employed mice with inactivated IL-6 gene (IL-6 KO) and analyzed their response to LPS challenge, using the RotaRod performance test. In contrast to wild type (WT) mice, IL-6 KO animals were completely protectedfrom inflammation-induced endurance loss after systemic (i.p.) LPS administration. Since IL-6 may affect both muscle metabolism and behavior we aimed to establish, which of these effects account for LPS-induced IL-6-mediated endurance loss. To answer thisquestion, we tested WT and IL-6 KO mice using the RotaRod following local intramuscular (i.m.) or systemic (i.p.) administration of LPS. WT mice showed moderate reduction of endurance after i.m. LPS treatment. Strikingly, IL-6 KO mice, despite being fullyprotected from systemic LPS-induced endurance loss, demonstrated a significant reduction in performance on RotaRod following local induction of inflammation in the muscles. Altogether our data suggest the dual role of IL-6 in inflammation-induced fatigue and indicate that anti-IL-6 therapy may be beneficial for patients with systemic inflammatory response.