Testosterone-Induced Effects on Lipids and Inflammation

Abstract

Chronic pain has to be considered in all respects a debilitating disease and 10–20% of the world's adult population is affected by this disease. In the most general terms, pain is symptomatic of some form of dysfunction and (often) the resulting inflammatory processes in the body. In the study of pain, great attention has been paid to the possible involvement of gonadal hormones, especially in recent years. In particular, testosterone, the main androgen, is thought to play a beneficial, protective role in the body. Other important elements to be related to pain, inflammation, and hormones are lipids, heterogenic molecules whose altered metabolism is often accompanied by the release of interleukins, and lipid-derived proinflammatory mediators. Here we report data on interactions often not considered in chronic pain mechanisms.

Long‐term testosterone depletion attenuates inflammatory bone resorption in the ligature‐induced periodontal disease model

“…Sustained increased production of high levels of proinflammatory mediators in the local microenvironment triggers a cascade of events that, in some individuals, results in extensive and irreversible degradation of both mineralized and non‐mineralized connective tissues of the periodontium . The biological activity of various cytokines and inflammatory mediators in the periodontal microenvironment may be directly related to the extent and severity of periodontal tissue destruction; however, the very production of these mediators can be influenced by environmental, genetic and systemic factors, including changes in the serum levels of sexual hormones, which are potent modulators of inflammation . In fact, our research group has reported on the influence of testosterone on bone tissue in association with the regulation of local production of cytokines …”

“…These mediators indirectly mediate degradation of non‐mineralized and mineralized tissue degradation by inducing the production of matrix metalloproteases and osteoclast‐inducing and activating receptor activator of nuclear factor kappa‐B ligand (RANKL), resulting in the resorption of the alveolar bone . In this context, steroid hormones, including sex hormones, are potent modulators of inflammation and bone turnover . Testosterone has an immunossupressive effect, as indicated by the decrease of macrophage and lymphocyte T helper (CD4+ T) cell infiltration in experimental autoimmune orchitis in rats, and these effects were associated with reduced production of proinflammatory mediators monocyte chemoattractant protein‐1 (MCP‐1), TNF, IL‐6 and IFN‐ in the draining lymph nodes .…”

“…Testosterone has an immunossupressive effect, as indicated by the decrease of macrophage and lymphocyte T helper (CD4+ T) cell infiltration in experimental autoimmune orchitis in rats, and these effects were associated with reduced production of proinflammatory mediators monocyte chemoattractant protein‐1 (MCP‐1), TNF, IL‐6 and IFN‐ in the draining lymph nodes . Moreover, in vitro, treatment of näive T cells with testosterone expanded the suppressive T regulatory subset . Production of IL‐1β and TNF by human macrophages in response to oxidized low‐density lipoproteins was also reduced by testosterone; whereas in murine macrophages testosterone downregulated lipopolysaccharide (LPS)‐induced activation of protooncogen c‐FOS, p38 mitogen‐activated protein kinases (p38 MAPK) and reduced the production of nitric oxide synthase (NOS) .…”

Testosterone therapy in men with Crohn’s disease improves the clinical course of the disease: data from long-term observational registry study

“…The disease is characterized by intestinal inflammation which leads to progressive bowel damage, increasing disability and a loss of quality of life, and the treatment is cumbersome. In recent years, a significant role of testosterone as an immune modulator [3] in a large number of disease entities such as cardiovascular disease [41], rheumatoid arthritis [42] or inflammatory processes of the central nervous system [43] has become apparent.…”

“…Inflammatory processes play a significant role in the etiology of cardiovascular disease, and testosterone shows anti-inflammatory effects [1]. Several studies have documented that low testosterone levels are associated with an increase in inflammatory factors and that administration reduces their levels (for review [2,3]). There is evidence showing an immunomodulatory and protective effect of testosterone in a model of chronic testicular inflammation and testosterone as a new factor in the differentiation of regulatory T cells [4].…”