Metamizole modulates the concentrations of cytokines and hematopoietic growth factors in an experimental model of depression

Objective: In recent years, evidence of antidepressant-like activity of non-steroidal anti-inflammatory drugs has been presented. Furthermore, associations between cytokines, which are important components of the immune system, as well as hematopoietic growth factors and depression have also been demonstrated. In this study, it was aimed to analyze the effect of metamizole on the expression of cytokines and hematopoietic growth factors in mice exposed to unpredictable stress models. Method: In order to develop chronic depression behaviors, an unpredictable chronic mild stress model was applied to mice. The depression group was not given any drug and other groups were given 100 and 200 mg/kg metamizole. Forced swimming test was performed to evaluate the effect of metamizole against depression. Relative concentrations of interleukin-1 alpha (IL-1α), IL-1 beta (IL-1-ß), IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, Interferon gamma (IFN-γ)-, tumor necrosis factor-alpha (TNF-α), Granulocyte-colony-stimulating factor (G-CSF), and Granulocyte-macrophage colony-stimulating factor (GM-CSF) were analyzed in serum samples of animals with semi-quantitative ELISA. Results: In the forced swimming test, the immobility time of the depression group significantly increased compared to the control group. The immobility time of groups treated with metamizole significantly decreased compared to the depression group and approached the control. Significant decreases were observed in the relative concentration levels of cytokines and hematopoietic growth factors in the groups treated with 100 and/or 200 mg/kg metamizole compared to the depression group except for IL-1α, IL-4, and IL-10. Conclusion: Evidence showing the contribution of COX enzymes to the pathophysiology of depression is increasing. In this context, the results indicate that metamizole, which can inhibit both isoforms of COX, may cause changes in cytokine levels and hematopoietic growth factors in a depression model. However, more controlled clinical studies are needed.