Simultaneously, it was shown that major depression is accompanied by a chronic low-grade inflammatory response as indicated by increased levels of macrophage M1-related pro-inflammatory cytokines, including IL-1β and tumor necrosis factor (TNF)α, the soluble IL-1 receptor antagonist (sIL-1RA), increased IL-6 trans-signaling (that is increased IL-6 and sIL-6R levels), and increases in positive acute phase proteins, such as haptoglobin, and complement factors (Maes et al. 1991, 1992b, 1994, 1995a, b; Słuzewska et al. 1995; Frommberger et al. 1997; Mikova et al. 2001). This evidence concerns the gene TNF and major depressive disorder.