Cytokines In Major Depression And

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Among the immune-inflammatory markers studied in depression there are the pro-inflamatory cytokine IL-6, soluble IL-6 receptor (sIL-6R), and soluble interleukin-2 receptor (sIL-2R) as well as soluble transferrin receptor (sTfR). Maes et al. (1995a) and Sluzewska et al. (1995a, 1996b) found significantly elevated concentrations of all the above-mentioned cytokines and soluble receptors in acute depressive episodes. Furthermore, Maes et al. (1995a) observed this too in clinical remission patients in comparison with normal controls. The soluble form of the IL-6 receptor (sIL-6R) is the only soluble interleukin receptor which, after combining with IL-6, intensifies its bio-activity (Bock et al., 1992). As an index of the potentiating effects of plasma sIL-6R on IL-6, the product term: sIL-6R x IL-6 is computed in clinical studies. In our previous study (Sluzewska et al., 1996b), we demonstrated that the value of the product term was three times higher in depressed patients than in healthy controls.

It was recently reported by Sluzewska et al. (1995b) that TRD patients have specially elevated concentrations of IL-6, sIL-6R, and the product term in comparison with responders-to-pharmacological treatment. These results correspond with those obtained from 33 TRD hospitalized patients in our Department during the last 20 months (Sluzewska et al., unpublished data) in whom we have found elevated levels of IL-6, sIL-6R, product term, sIL-2R, and sTfR. There was a significant correlation between AGP and IL-6 in TRD patients (Sluzewska et al., 1995b) as well as between AGP, ACT, and IL-6 in 33 TRD patients, hospitalized in Department of Adult Psychiatry in Poznan during the year of 1995 (Sluzewska et al., 1997b).

Depression is also accompanied by significantly increased plasma levels of the IL-1 receptor antagonist (IL-1RA) (Maes et al., 1997; Sluzewska et al., 1997e, submitted). IL-1RA is a pure IL-1 receptor antagonist (Dripps et al., 1991) that inhibits the biological activities of IL-1 at target cells (Dayer and Burger, 1994). It is mainly derived from monocyte/macrophage lineage (Dinarello, 1994) and released in vivo during an AP response (Dayer and Burger, 1994).

IL-1 and IL-6 are pleotropic cytokines that mediate the primary host response during the apr following infection or injury (Heinrich et al., 1990). These cytokines are predominantly released by cells of the macrophage/monocytic arm of CMI, and in lower amounts also by T and B lymphocytes (Wolvekamp and Marquet, 1990).

Changes in the concentration of cytokines (especially IL-6, its soluble receptor and IL-1RA) as well as glucocorticoids during depression may be involved in the regulation of AGP and ACT glycosylation. It has been shown that IL-6 exerts a direct effect on type I and type II glycosylation of apps (Van Dijk et al. 1994). Glucocorticoids modulate the effects of cytokines on glycosylation of apps. Van Dijk and Mackie-wicz (1993) found in vivo and in vitro studies indicating that the magnitude and type of glycosylation alterations are dependent on the composition and the amount of interacting cytokines; these effects can be further modulated by treatment with the synthetic glucocorticoid dexamethasone. Morover, Pos et al. (1988) showed that dexamethasone treatment in vivo resulted in the increase of serum concentrations of type I glycosylation forms of AGP and Hp.

One of the indicators of activation of T lymphocytic arm of the CMI is the presence of soluble CD8 in plasma. In 33 TRD patients studied, increased plasma concentration of sCD8 was found (Sluzewska et al., unpublished). The sCD8 molecule or suppressor/cytotoxic T cell antigen is secreted by activated T lymphocytes such as CD8+T cells (Tomkinson et al., 1989). A positive relationship between increased levels of sIL-2R and sCD8 is frequently observed in immune disorders (Linker-Israeli et al., 1994).

The sIL-2R is released by activated T cells into the circulation and plasma concentrations of sIl-2R correlate well with in vivo IL-2 production (Caruso et al., 1993). Increased concentrations of sIL-2R in depressed patients were reported by Maes et al. (1995a) and Sluzewska et al. (1996b).

The TfR is an activation marker (CD 71) for lymphocytes, whose expression is tightly coupled to the IL-2R (Woith et al., 1993). Increased plasma concentration of sTfR in major depressed patients were found by Maes et al. (1995a) and Sluzewska et al. (1996b).

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Natural Depression Cures

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