TNF and major depressive disorder: Nukina et al. (2001) tested whether stress leads to elevated plasma IL-6 in mice and found that plasma IL-6 was elevated in mice after 1 h of stress and that elevated IL-6 may lead to HPA axis dysfunction, altered synaptic neurotransmission, and reduced neurotrophic factors, which are indirectly involved in the pathogenesis of depression. It has been shown that depressive symptoms in depressed patients can be improved by lowering serum TNF-α levels, which in turn improves sleep (Postal and Appenzeller, 2015).