Common mechanisms involved in lung cancer and depression: The dominant role of interleukin-6-IDO pathway in the lung-brain axis

A higher prevalence of depression occurs in patients with lung cancer, while poor prognosis of lung cancer is often associated with depression. Excessive inflammatory response is one of the factors in the presumptive etiology of depression, and the inflammatory microenvironment also plays a key role in tumor genesis, which may indicate a common factor between the lung and the brain. Recently, a new hypothesis, called lung-brain axis, has been proposed because critical pulmonary disorders, such as acute lung injury and acute respiratory distress syndrome appear to be responsible for mood disorder and poor cognitive outcomes. Thus, lung cancer and depression might influence each other through the lung-brain axis. Findings throughout the literature suggest that activation of the interleukin (IL)-6 pathway can activate glial M1 and A1 phenotype activity, which triggers the activity of indoleamine 2,3-dioxygenase (IDO), thereby depleting tryptophan and reducing 5-hydroxytryptamine (5-HT) synthesis. The activation of IL-6 can also inhibit the expression of the 5-HT transporter through the IL-6-JAK/STAT signaling pathway. These changes are major neuropathological aspects of depression. The pathway, as mentioned above, can also promote lung cancer since increased IDO inhibits T lymphocyte proliferation and induces lymphocyte apoptosis. Therefore, the up-regulation of IDO caused by IL-6 may be the common cause for both the development of depression and lung cancer. The purpose of this review is to analyze the inflammatory mechanism and the role of the lung-brain axis in these two disease entities. The review aims to confirm the hypothesis of the lung-brain axis and promote our understanding of the interaction between the lung and the brain.