Potential role of lymphotoxin-alpha (tumor necrosis factor-beta) in the development of schizophrenia

Among cytokines, the immunomodulatory functions of lymphotoxin-alpha (tumor necrosis factor (TNF)-β) is well known and could come up with the pathophysiology of schziophrenia. It affects and modulates production of other cytokines such as TNF-α and IL-6 which are consistently proposed to be involved in the development of schizophrenia. TNF-β is also crucial to prevent prenatal infections. In addition, TNF-β is effective in the protection of neuronal cells against glutamate and NMDA toxicity which is considered a neurodevelopmental hypothesis of schizophrenia. Moreover, it was also found to be associated with the regulation of glial cells and stimulation of the synthesis and secretion of nerve growth factors (NGFs) in the CNS. Finally, TNF-β gene is located on the short arm of chromosome 6 (6p21.1-6p21.3), where is a possible susceptibility locus for schizophrenia. Therefore, TNF-β may provide a new insight for understanding schizophrenia, providing a more systematic organization of immunological contributing factors to the development of schizophrenia.