Abstract
The negative relationship between testosterone and inflammatory cytokines has been reported for decades, although the exact mechanisms of their interactions are still not clear. At the same time, little is known about the relation between androgens and acute phase proteins. Therefore, in this investigation, we aimed to study the relationship between androgen status and inflammatory acute phase reactants in a group of men using multi-linear regression analysis. Venous blood samples were taken from 149 men ranging in age from 18 to 77 years. Gonadal androgens [testosterone (T) and free testosterone (fT)], acute phase reactants [C-reactive protein (CRP), ferritin (FER), alpha-1-acid glycoprotein (AAG), and interleukin-6 (IL-6)], cortisol (C), and lipid profile concentrations were determined. It was demonstrated that the markers of T and fT were negatively correlated with all acute phase proteins (CRP, FER, and AAG; p < 0.02) and the blood lipid profile [total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG); p < 0.03]. Multivariate analysis showed that T, fT, and the fT/C ratio were inversely correlated with the CRP, AAG, and FER concentrations independently of age and blood lipids. When adjustment for BMI was made, T, fT, and the fT/C ratio were negatively correlated with the AAG concentrations only. In addition, it was demonstrated that gonadal androgens were positively correlated with physical activity level (p < 0.01). We have concluded that a lowered serum T concentration may promote inflammatory processes independently of adipose tissue and age through a reduced inhibition of inflammatory cytokine synthesis, which leads to enhanced acute phase protein production. Therefore, a low serum T concentration appears to be an independent risk factor in the development of atherosclerosis and cardiovascular diseases. Moreover, the positive correlation between testosterone and physical activity level suggests that exercise training attenuates the age-related decrease in gonadal androgens and, in this way, may reduce the enhancement of systemic low-grade inflammation in aging men.
Highlights
Age-related upregulation of the inflammatory response [1] and the worsening of the blood lipid profile are of great importance because these changes are linked to atherosclerosis, enhanced cardiovascular risk, and the development of metabolic syndrome
We aimed to study the relationship between androgen status and inflammatory acute phase reactants (CRP, FER, and alpha-1-acid glycoprotein (AAG)) in a moderately large group of men using multi-linear regression analysis
Only one subject presented with T and fT concentrations slightly below the healthy adult male reference ranges, but even in this case, a late-onset hypogonadism (LOH) syndrome was not diagnosed because there were no symptoms suggestive of testosterone deficiency [see, e.g., [13]]
Summary
Age-related upregulation of the inflammatory response (described as “inflamm-aging”) [1] and the worsening of the blood lipid profile are of great importance because these changes are linked to atherosclerosis, enhanced cardiovascular risk, and the development of metabolic syndrome. Connections between testosterone and the inflammatory process have been widely studied [for a review, see [4]], the existence of the bidirectional mechanisms between the immune and endocrine systems was reported at least 20 years ago [5]. This concept has a strong scientific foundation since androgens have been shown to regulate the inflammatory response [6] by suppressing pro-inflammatory leukotriene biosynthesis [7], decreasing pro-inflammatory mediators, and increasing anti-inflammatory cytokines, leading to a state of reduced inflammation [8]. An inflammatory process as a manifestation of increased oxidative stress may negatively influence the androgen level [9], both through direct disruption of the reproductive tissue and through the detrimental effect on the regulatory mechanisms of the hypothalamic–pituitary– gonadal (HPG) axis
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