Inflammation and major depression: a role of Th1/Th2 shift on the neuroimmune interactions and its relevance in cancer prognosis

FRICK LUCIANA ROMINA

Buenos Aires

Congreso; 15th World Congress on Psychiatry; 2011

World Psychiatry Association

Inflammation and depression are reciprocally interconnected. Patients suffering major depression display decreased levels of Th1 cytokines, whereas Th2 cytokines are elevated. In addition, subjects treated with recombinant cytokines often develop depressive disorders, revealing a bidirectional cross-talk between the nervous and the immune system. This neuro-immune interaction and chronic inflammation status is proposed to be in part responsible for the onset of certain types of cancer. We are exploring this hypothesis using animal models of depression. Using chronic stress models of depression in mice, we found a shift from Th1 to Th2, accompanying reductions of T-cell response to mitogens and alterations of CD4+/CD8+ ratio. Also, tumors grow faster in depressed mice, and show an increase of the proliferation/apoptosis balance (PCNA/active caspase-3 immunoreactive cells). Moreover, a differential gene expression of cell division and death markers was observed. Cyclins D1 and B were increased in tumors from stressed animals, whereas the tumor suppressor p53 and PTEN, and the cell cycle inhibitors p16/INK4A and p27/Kip1 were decreased. Also, the expression of the proapoptotic factor Bcl-2 and the antiapoptotic factors Bax and Bad were lower and higher respectively in these animals. Interestingly, IFN-ã and IL-2 as well as total CD4+ counts were reduced in tumor bearing animals from the depression model group. Therefore, given the causal relation between the immune response and the alterations in the cell cycle and apoptosis of tumors, we propose that the Th1/Th2 shift observed herein could be responsible of the influence of major depression on the prognosis of cancer.