32-39 Increased numbers of peripheral mononuclear cells in MD have been described by different groups of researchers.40 Neopterin is a sensitive marker of the cell-mediated type-1 immunity. The main sources of neopterin are monocytes/macrophages. In accordance with the findings of increased monocytes/macrophages, an increased secretion of neopterin has been described by several groups Inhibitors,research,lifescience,medical of researchers.41,42 The increased plasma concentrations of the proinflammatory cytokines IL-1 and IL-6 observed in depressed patients was found to correlate with the severity of depression and with measures of the hypothalamus-pituitary-adrenal (HPA)-axis hyperactivity.43,44

As genetics plays a role in MD, the genetics of the immune system in relation to MD has also been investigated. Particular cytokine gene polymorphisms, eg, in genes coding for IL1 and TNF-α may confer a greater susceptibility to develop MD, although studies are conflicting.45,46 The production of IL-2 Inhibitors,research,lifescience,medical and IFN-γ is the typical marker of a type-1 immune response. In contrast to schizophrenia, IFN-γ is produced Inhibitors,research,lifescience,medical in greater amounts by lymphocytes of patients with MD than of healthy controls.42,45 Higher plasma levels of IFN-γ in depressed patients, click here accompanied by lower plasma tryptophan availability were described,42 and the IFNγ/IL-4 ratio, a marker for

Thl/Th2 balance is also higher in depressed patients.45 Data on IL-2 in MD are mainly restricted to the estimation of its soluble receptor sIL-2R in the peripheral blood. Increased sIL-2R levels reflect an increased production of IL-2. The blood levels of sIL-2R were repeatedly found to be increased Inhibitors,research,lifescience,medical in MD patients.39 Increased expression of ICAM-1 is observed in inflammatory processes, and promotes the influx of peripheral immune cells through the blood-brain barrier.47 By this mechanism, macrophages and costimulatory lymphocytes Inhibitors,research,lifescience,medical can invade the central nervous system (CNS), further

increasing the proinflammatory immune response. The plasma levels and CNS expression of ICAM-1 are associated with depressive symptoms in patients treated with IFN-γ. Increased sICAM-1 levels were observed in patients with more depressive symptoms,48 and increased expression of ICAM-1 was found in the prefrontal cortex of Astemizole elderly depressed patients.49 In late -life depression, however, there are conflicting results.50 Since different pathologies may underlie the syndrome of depression, different immunological states might be involved. Indeed, different types of MD were observed to exhibit different immune profiles: the subgroup of melancholic depressed patients showed a decreased type-1 activation – as observed in schizophrenic patients40 – while the nonmelancholic depressed patients showed signs of inflammation such as increased monocyte count and increased levels of α2-macroglobulin.