Fig. 6: Combination drug treatment reduces peripheral inflammation.
a–d, Histopathological analysis of inflammation in kidney (a,b) and WAT (c,d) of 24-month-old female mice (a,c) and male mice (b,d). Combination-treated female mice and male mice showed significantly reduced kidney inflammation compared to control and trametinib-treated animals. Linear regression. Numbers in brackets indicate the number of tissue samples from independent mice per treatment. There was a non-significant trend for reduced WAT inflammation upon treatment with rapamycin and rapamycin/trametinib. e–p, Plasma protein levels of circulating cytokines as measured by the Olink Target 96 Mouse Exploratory panel: Tnf (e,f), IL17a (g,h), IL23r (i,j), Tgfα (k,l), IL6 (m,n) and IL10 (o,p). Drug effects on plasma cytokine levels were highly sex specific, with Tnf, IL17a, IL23r and Tgfα being downregulated by the combination treatment only in female mice but not male mice. One-way ANOVA with Tukeyʼs post hoc test. Numbers in brackets indicate the number of plasma samples from independent mice per treatment. Data in e and p are presented as mean ± s.e.m. Inflammation and plasma cytokine data for control and rapamycin-treated animals were previously published22.
