SNRI effective treatment does not restore changes of immune and inflammatory parameters in depressed patients

Introduction: It has been hypothesized that major depression may be accompanied by alterations in cell-mediated and humoral immunity. Moreover, major depression appears to be associated with increased plasma concentrations of positive `acute-phase' proteins and increased production of cytokines. It has been suggested that an altered production of cytokines may underpin many changes of immune or inflammatory markers which have been observed. Our aim was to determine plasma concentrations of interleukin 6 (IL-6), soluble interleukin 6 receptor (sIL6R), Tumor Necrosis Factor (TNF-α) and C reactive protein (CRP) in patients with major depression in an acute phase of illness and after 12 weeks of antidepressant treatment with SNRIs. Methods: 24 outpatients (M/F = 8/16; mean age 46.79±12.97) with a Major Depressive Disorder (MDD) during a Major Depressive Episode (MDE) and 20 healthy controls (M/F = 8/12, mean age = 40.05±11.02) have been recruited at the Institute of Psychiatry of the Catholic University in Rome. The severity of depression was assessed with the 21-item HDRS, anhedonia and retardation scores were evaluated by Snaith-Hamilton Pleasure Scale (SHAPS) and Depression Retardation Rating Scale (DRRS). Blood samples for the determination of C-reactive protein, TNF-alpha, IL-6 and sIL-6R were collected. Cytokines were measured using commercial enzyme linked immunosorbent assays (ELISA). Levels of C-reactive protein were measured using an immunoturbidimetric assay. Following baseline investigation all patients were treated with either venlafaxine (150–225 mg) or duloxetine (60–120 mg). Psychopathological status and laboratory testing were assessed before the admission and at the end of the study, after 12 weeks. Results: Plasma concentrations of IL-6 (0.59±1.14 vs. 0.06±0.27 pg/ml) and CRP (3.28±3.59 vs. 1.33±1.48 mg/ml) were significantly higher in depressed patients than in healthy controls. sIL-6R and the product of IL-6 and sIL6R were higher but not significantly. There was no difference in plasma concentrations of TNF-α between depressed patients and healthy controls. A significant positive correlation between CRP and IL-6 (r = 0.25, p = 0.047) has been observed. All patients significantly improved after treatment and most of them (62.5%) achieved a full remission. Finally, antidepressant treatment with SNRIs did not significantly change plasma IL-6, sIL-6R, TNF-α, CRP. Conclusions: Changes of plasmatic levels of IL-6 and CRP in depressed patients are consistent with previous findings. Despite the clinical efficacy SNRIs did not appear to have a significant effect on immune parameters in major depression. Our finding is in contrast with O'Brien et coll. that observed a significant drop of C-reactive protein after SSRIs and showed an anti-inflammatory response independent of antidepressive action. The immune alteration in major depression seems to be trait rather than state associated and the inflammation response could not be directly involved in the pathophysiology of depression. The efficacy of antidepressant treatment may reflect indirect immunomodulatory effects rather than a direct down-regulation of inflammatory response activation. Further researches in larger samples are needed to clarify the involvement of immune variables in major depression and the influence of SNRIs.