In accordance with this “cytokine hypothesis of depression”, we examined how short-term irisin injections may affect the cytokine profile in the hippocampus and the PFC by analyzing the expression of pro- (IL-6 and IL-1β) and anti-inflammatory (IL-4, IL-10, and IL-1ra) cytokines majorly involved in MDD. This evidence concerns the gene FNDC5 and depressive disorder.