Fig. 4

Preventive effect of rapamycin–metformin combination in obese mice with collagen-induced arthritis (CIA). a Rapamycin–metformin reduced the arthritis score and incidence. b Histological features of joints; images were stained with hematoxylin and eosin and safranin O. Original magnifications, × 40 and × 200. c IL-1β, IL-6, IL-17, and TNF-α levels in joint-tissue sections. Each cytokine-positive cells in the total cell number were counted and graphed. Original magnification, × 400. In vivo animal experiments were conducted five times per group. Tissues were analyzed from five mice of each group. Data represent the mean ± SD. *P < 0.05 and **P < 0.01