40. Antidepressant effects of macrophage migration inhibitory factor using a knockout mouse approach

It has been established that depressed patients display immune alterations. Recently, it was reported that plasma levels of the cytokine macrophage migration inhibitory factor (MIF) correlate positively with depression scores. In the current study we wished to examine the relationship between MIF and depression using MIF knockout (KO) mice and wildtype littermates. Male and female KO and wildtype mice were tested for anhedonia in the sucrose preference test (SPT), and despair in the forced swim test (FST) and tail suspension test (TST). Brain mRNA expression of IL-1β and IL-6 was subsequently examined using RT qPCR and protein-levels of IL-1β, IL-12p70, IFN-γ, IL-6, KC, IL-10 and TNF-α was measured using high-sensitivity electrochemiluminescence-based multiplex immunoassays. Results showed a significant genotype X sex interaction in SPT, with male KOs showing increased sucrose preference compared to controls. A similar interaction was found for FST, where male KOs showed decreased immobility. In TST KOs showed decreased immobility. A positive correlation was found between IL-6 mRNA and stillness in TST. Furthermore, KO mice showed decreased levels of IFN-γ. Our results suggest that MIF gene deletion has clear antidepressant effects, possibly mediated by the suppression of IFN-γ in the KO animals. These data support the growing line of evidence for an involvement of inflammatory-factors in depression and further suggests that MIF ligands have potential as antidepressants. [ABSTRACT FROM AUTHOR]