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Recently, it was reported that there may be an activation of the inflammatory response system in detoxified alcohol-dependent patients without apparent liver disease (AWLD). The aims of the present study were to examine serum zinc (Zn) concentrations, total serum protein (TSP) and patterns obtained in the electrophoretically separated protein fractions in relation to serum interleukin-6 (IL-6) and IL-8 concentrations in detoxified AWLD patients. Zn, TSP, SP electrophoresis, and serum IL-6 and IL-8 concentrations were determined in detoxified AWLD patients and age-matched healthy volunteers. Serum Zn, TSP and the serum concentrations of albumin (Alb) and the β fraction were significantly lower in detoxified AWLD patients than in healthy volunteers. The percentage of the α<sub>2</sub> fraction was significantly higher in detoxified AWLD patients. Lower serum Zn in detoxified AWLD patients was attributable to lowered serum Alb. Lower serum Alb was significantly and negatively correlated to increased serum IL-8. The percentage of the α<sub>1</sub> and α<sub>2</sub> fractions were significantly and positively related to serum IL-6 and IL-8. The results show that there is an in vivo activation of the inflammatory response system in detoxified AWLD patients and that lower serum Zn may be causally related to lower serum Alb.

Abstract Background Major depressive disorder (MDD) involves disturbances in neuroimmune–metabolic and oxidative stress (NIMETOX) pathways. However, oxidized HDL (OxHDL) and oxidized LDL (OxLDL) have not been examined together. Methods Serum OxHDL, OxLDL, and a panel of oxidative, antioxidant, and acute phase inflammatory (API) biomarkers were measured in 125 Chinese MDD patients and 40 healthy controls using ELISA and spectrophotometry. Results MDD patients showed increased OxHDL, reduced OxLDL, and markedly lowered antioxidant defenses, while classical lipid peroxidation markers remained unchanged. These alterations were independent of metabolic syndrome. The acute phase response was closely linked to reductions in HDL-related antioxidants and OxLDL. A combined biomarker model including the HDL/OxHDL ratio, apolipoprotein (ApoA)1, OxHDL, OxLDL, lipid hydroperoxides, and API index achieved an area under the ROC curve of 0.915 (SE=0.023) and a cross-validated sensitivity of 83.1% with 84.6% specificity. The variance in overall severity of depression, physiosomatic symptoms and recurrence of illness was to a large extent explained by oxidative/antioxidant biomarkers. The top-most important biomarkers were OxHDL/OxLDL (increased) and antioxidant (decreased) levels. Conclusion Increased OxHDL is a key component of MDD, indicating structural and dysfunctional HDL particles and oxidative damage to its major structural protein (ApoA1). HDL particles rather than LDL particles and other lipids are the most vulnerable sites to be attacked by oxidative stress and inflammatory processes in MDD. These data support the view that increased oxidative damage to HDL particles is a key process in MDD. Preventing HDL particle oxidation is a major new drug target in MDD.

To examine immune-inflammatory and oxidative (I&O) biomarkers in major depression (MDD) and its related phenotypes, we recruited 114 well-phenotyped depressed patients and 50 healthy controls and measured serum levels of interleukin (IL)-1α, soluble IL-1 receptor antagonist (sIL-1RA), soluble IL-2 receptor (sIL-2R), soluble IL-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 60 and 80 kDa (sTNF-R1/R2), and thiobarbituric acid reactive substances (TBARS). Obtained results indicate that MDD is characterized by increased sIL-1RA, sTNF-R1, and TBARS concentrations. Melancholic depression is associated with increased sIL-6R but lowered IL-1α levels. A current episode of depression is accompanied by significantly increased sIL-6R compared to the remitted state. Treatment-resistant depression (TRD) is accompanied by increased sIL-6R and TBARS but lowered sTNF-R2 levels compared to non-TRD patients. These immune markers are not significantly correlated with Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Scale (MADRS), number episodes, or age at onset. Our findings show that increased sIL-1RA, sTNF-R1, and TBARS levels may be trait markers of depression, while increased sIL-6R levels may be a state marker of melancholia and an acute phase of depression. MDD is accompanied by increased lipid peroxidation and simultaneous activation of immune pathways, and the compensatory anti-inflammatory reflex system (CIRS). TRD is characterized by highly increased oxidative stress and probably increased TNFα and IL-6 trans-signalling. Novel treatments for major depression should target oxidative stress pathways, while new treatments for TRD should primary target lipid peroxidation and also activated immune-inflammatory pathways.