Cytokines And The Hpa Axis In Major Depression And

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Several findings suggest the existence of an HPA axis hyperactivity in TRD (Christiansen et al.. 1989: Me Leod. 1972: Amsterdam et al.. 1983.1994V Conseauentlv.

in 60 major depressed inpatients from the Department of Adult Psychiatry in Poznan, all Caucasians with and without melancholia, the DST test was performed (Sluzewska et al., 1995b). Among those patients with an abnormal DST response, the concentrations of AGP were significantly higher than in the DST suppressors. Pathological results were observed in 33% of the patients and among them 38% suffered fromTRD. In our previous study, a significant correlation between morning plasma Cortisol levels and levels of AGP was found in the depressed patients, which could suggest an effect of glucocorticoides on AGP synthesis (Sluzewska and Rybakowski, 1993). Recent data obtained from 33 TRD patients (Sluzewska et al., 1997c) reveal a significant positive correlation between the morning plasma Cortisol levels and the plasma concentrations of IL-6, sIL-2R, AGP, ACT. Further, Maes et al. (1995c) found positive correlations between IL-6, as well as sIL-2R, and Cortisol in major depressed patients, and in combined group of major depressed and healthy controls.

From the studies of Navarra et al. (1991) and Tominga et al. (1991), there is evidence that IL-6, at concentrations known to occur in human plasma (Navarra et al., 1991; Naitoh et al., 1988), exerts a potent effect on the HPA axis by stimulating the secretion of CRH and ACTH and steroidogenesis. However, as pointed out by Fukata et al. (1993), the detection of any particular cytokine in the blood does not necessarily means that this entity assumes a role as an immune-derived mediator that causes hyperglucocorticoidemia, even when the entity is known to be effective.

The above-presented data may suggest that changes in the concentration and microheterogeneity of AGP and ACT in depressed patients and especially in TRD patients could be related to both HPA axis pathology and increased production of cytokines (especially pro-inflammatory cytokines such as IL-6 and its sIL-6R, as well as IL-1). Futhermore, these abnormalities may be connected with the observed "refractoriness" of the depressive state to the antidepressant treatment.

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