152 IL-6 may be involved in the modulation of the HPA axis.153 Activation of the HPA axis is one of the best-documented changes in MD.154 Furthermore, the relationship MG-132 cell line between psychological or physical stress and an enhanced IL-6 secretion in the peripheral immune system seems to be well established.155-158 Impaired stress coping Inhibitors,research,lifescience,medical is often observed in depressed patients. Thus, the high number of reports of elevated peripheral IL-6 levels in MD patients may be related to psychological stress. On the other hand, there is evidence for a relationship between high peripheral IL-6 levels and elevated CNS 5-HT availability.

IV or IP administration of IL-6 induced not only an activation of the HPA axis, but also an increase in brain tryptophan and 5-HT metabolism, whereas the norepinephrine metabolism was unaffected.113

Accordingly, IL-6 seems to mediate the activation of the HPA axis and the 5-HT CNS after administration of the endotoxin LPS.112 Thus, elevated plasma levels of IL-6 do not fit with the hypothesis of a Inhibitors,research,lifescience,medical 5-HT deficiency in MD. Rather, it should be recognized that an inherent heterogeneity exists in the etiology of depression and different neurotransmitter systems may be disturbed. On the basis of the commonly accepted Inhibitors,research,lifescience,medical idea that MD may be a heterogeneous group of disease entities, the group of Arolt and Rothermundt investigated the difference between melancholic and nonmelancholic MD regarding their cytokine expression patterns.159 They detected profound differences between these diagnostic subgroups: nonmelancholic patients showed increased counts of leukocytes, lymphocytes, and natural killer (NK) cells in the acute stage of

disease Inhibitors,research,lifescience,medical and after 2 and 4 weeks of treatment. However, their in vitro production of the cytokines IL-2, IL-10, and IFN-γ was unchanged compared with that of healthy controls. Melancholic patients on the other hand demonstrated normal Inhibitors,research,lifescience,medical cell counts, but a decreased in vitro production of IL-2, IFN-γ, and IL-10 during the acute stage of disease. Following clinical improvement, cytokine production patterns normalized in these patients. Schizophrenia A pathophysiological role of cytokines is also discussed in the other major psychiatric disorder, schizophrenia. The reports of the psychotic symptoms inducing effects of IL-2 in cancer patients attracted attention GPX6 of this Th1-like cytokine to the immunopsychiatric schizophrenia research. Early studies reported elevated IL-2 levels in cerebrospinal fluid of schizophrenia patients,160,161 but others failed to replicate these intriguing findings.162-165 IL-2 levels in serum were reported to be either increased166 or decreased.167 A significant decrease in the production of IL-2 by peripheral lymphocytes is one of the best-replicated immunological findings in schizophrenia.