Combined interleukin-6 and interleukin-1 deficiency causes obesity in young mice

Abstract

Proinflammatory cytokines including interleukin (IL)-1 and IL-6 exert pleiotropic effects on the neuro-immuno-endocrine system. Previously, we showed that IL-1 receptor antagonist-deficient (IL-1Ra-/-) mice show a lean phenotype due to an abnormal lipid metabolism. On the contrary, it was reported that IL-6-/- mice exhibit obesity after 6 months of age. This study sought to assess the roles of IL-1 and IL-6 in body weight homeostasis. We generated mice deficient in IL-6 and IL-1Ra (IL-6-/- IL-1Ra -/-) and IL-6, IL-1α, and IL-1β (IL-6-/- IL-1-/-). IL-6-/- IL-1Ra-/- mice exhibited a lean phenotype, similar to IL-1Ra-/- mice. On the other hand, IL-6-/- IL-1-/- mice became obese as early as 10 weeks of age, while IL-1-/- mice and IL-6-/- mice were normal at this age. The daily food intake was significantly higher in IL-6-/- IL-1-/- mice than in IL-6-/- IL-1+/- mice, while energy expenditure was comparable in these two strains. Acute anorexia induced by peripheral administration of IL-1 was significantly suppressed in IL-6-/- IL-1-/- mice, but not in IL-1-/- mice or IL-6-/- mice compared with wild-type mice. These results indicate that IL-1 and IL-6 are both involved in the regulation of body fat in a redundant manner in young mice. © 2006 by the American Diabetes Association.