Psychoneuroimmunology and the cytokine action in the CNS: implications for psychiatric disorders.

1. Parallel to the current rapid development of new immunological methods, immune mechanisms are gaining more importance for our understanding of psychiatric disorders. The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system. 2. The topical literature dealing with the interactions of immune system, neurotransmitters, psychological processes, and psychiatric disorders, especially in relation to cytokines, is reviewed. 3. An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described. Cytokines, actively transported into the CNS, play a key role in this immune activation. It was recently observed that cytokines activate astrocytes and microglia cells, which in turn produce cytokines by a feedback mechanism. Moreover, they strongly influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. 4. There are indications that the cascade of cytokines can be activated by neuronal processes. These findings close a theoretical gap between stress and its influence on immunity. Psychomotor, sickness behavior and sleep are related to IL-1; disturbances of memory and cognitive impairment are to IL-2, in part also to TNF-alpha. The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia, and IL-6, on depressive disorders. 5. Although single cytokines most likely do not have a specificity for certain psychiatric disorders, a characteristic pattern of cytokine actions in the CNS, including influences of the cytokines on the blood-brain barrier, seems to play a role in psychiatric disorders. This may have therapeutic implications for the future.