Figure 7

Effect of HFD and tacrolimus on circulating levels of pro-inflammatory and anti-inflammatory cytokines at gd 4.5 in the HFD-dNONcNZO mice. As opposed to the metformin-treated mice, the systemic use of tacrolimus monotherapy resulted in a wide-range suppression of cytokines and chemokines in the blood of treated HFD-dNONcNZO mice. Depicted in (A–F) are bar graph representations of mean ± SDM of the fold changes in cytokines suppression by use of tacrolimus or metformin. Effect of treatment was analyzed by one-way ANOVA followed by Scheffe’s ad-hoc test. A 1.5-fold change in the protein expression of the cytokine relative to that of the NFD-NONcNZO mice was considered significant (p < 0.01 at 95% confidence, n = 3/phenotype). Of the most significantly inhibited serum cytokines by the use of tacrolimus (0.1 mg/kg) were IL1α, IL1β and IFNγ (A), IL12p70, IL17, IL23 and IL27 (B), IL2, TNFα and its downstream chemokine ligands TARC and TREM1 (C), IL6, IL4 and IL1rα (D), GM-CSF and the CXC ligands 9,10 and 11 (E), as well as the monocyte-macrophage regulatory chemokines MIP-1α (CCL3), MIP-1ß (CCL4) and MCP5 (CCL12) (F), respectively.