The Anti-Inflammatory Effects of Testosterone

Abstract

Low plasma testosterone (T) levels correlated with metabolic syndrome, cardiovascular diseases, and increased mortality risk. T exerts a significant effect on the regulation of adipose tissue accumulation, and in the glucose and lipids metabolism. Adipocytes are the primary source of the most important adipokines responsible for inflammation and chronic diseases. This review aims to analyze the possible effect of T on the regulation of the proinflammatory cytokines secretion. A systematic literature search on MEDLINE, Google Scholar, and Cochrane using the combination of the following keywords: "testosterone" with "inflammation," "cytokines," "adiponectin, CRP, IL-1B, IL-6, TNFα, leptin" was conducted. Sixteen articles related to the effect of low T level and 18 to the effect of T therapy on proinflammatory cytokine were found. T exerts a significant inhibitory effect on adipose tissue formation and the expression of various adipocytokines, such as leptin, TNF-α, IL-6, IL-1, and is positively correlated with adiponectin level, whereas a low T level is correlated with increased expression of markers of inflammation. Further studies are necessary to investigate the role of T, integrated with weight loss and physical activity, on its action on the mechanisms of production and regulation of proinflammatory cytokines.

Keywords: IL-6; adipokines; adiponectin; cytokines; inflammation; testosterone.

Figure 1.

T exerts its anti-inflammatory activity through different mechanisms. Firstly, T inhibits body fat expansion and reduces adipocytes size and metabolism. After its aromatization in estradiol, T can activate AR and ERα and ERβ, which contribute to adipocytes regulation decreasing the release of adipokines (leptin, IL-6, TNF-α, OPG, MCP-1α) and improving adiponectin and visfatin production, which possess an anti-inflammatory effect. Furthermore, T improves insulin activity and reduces the CRP from the liver. Altogether, it results in a reduction of inflammation and development of chronic disease.