Multiple mechanisms of cytokine action in neurodegenerative and psychiatric states: neurochemical and molecular substrates

Neuroinflammatory processes appear to play a fundamental role in the pathology associated with a number of neurodegenerative and psychiatric conditions. In this respect, the immunocompetent brain microglia and peripheral macrophages release a host of proinflammatory cytokines that not only modulate immunological processes but also influence neuronal functioning and even survival. For instance, alterations of the cytokines, tumor necrosis factor-alpha, as well as several of the interferons and interleukins have been associated with Parkinson's disease (PD) and clinical depression. Importantly, anti-inflammatory treatments that block these cytokines may impart protection against behavioural pathology and neuronal damage in animal models of PD and depression involving exposure to environmental toxins and stressors, respectively. The present review highlights the involvement of inflammatory cells and cytokines in depression and PD and explores some of the potential cellular and molecular mechanisms through which the immunotransmitters affect neuronal functioning. Attention is also devoted to the possibility that cytokines may sensitize neuroinflammatory pathways that, in turn, favour long-term pathology.