The influence of age and gender on serum dehydroepiandrosterone sulphate (DHEA-S), IL-6, IL-6 soluble receptor (IL-6 sR) and transforming growth factor beta 1 (TGF-beta1) levels in normal healthy blood donors

Abstract

Dysregulation of IL-6 synthesis is thought to play a role in the development of a number of age-related conditions, such as rheumatoid arthritis, osteoporosis, atherosclerosis, Alzheimer's disease and B cell malignancies. Recently it has been suggested that the production of IL-6 is influenced by the adrenal hormone dehydroepiandrosterone (DHEA) and its sulphated derivative DHEA-S. In humans we investigated the relationship between DHEA-S, IL-6, IL-6 sR and TGF-beta1 in the serum of normal healthy male and female blood donors. Using immunoassay techniques we found that the serum levels of DHEA-S significantly (P = 0.0001) decreased with age in both males and females. Furthermore, mean DHEA-S levels in all age groups were significantly (P = 0.0001) higher in males. Such correlations were not apparent for IL-6 using a standard assay, but a high sensitivity assay revealed that serum IL-6 was significantly (P = 0.0018) positively correlated with age in males only. In addition, serum levels of DHEA-S were significantly (P = 0.048) negatively correlated with serum IL-6, again in male subjects only. In contrast, serum IL-6 sR and TGF-beta1 levels were not correlated with age in either males or females and were not significantly different between the sexes. However, a significant (P = 0.024) negative correlation between DHEA-S and IL-6 sR was found in males. These studies clearly highlight the complex nature of the relationship between these molecules in the ageing process in normal healthy blood donors and demonstrate the need to use high sensitivity assays when measuring IL-6 in apparently healthy individuals under the age of 70 years.

Fig. 1

The correlation between serum DHEA-S levels and age in 412 male and 395 female healthy subjects. The individual values and regression lines are given. Note the highly significant negative correlation of DHEA-S with age in both males (r = −0.582, P = 0.0001) and females (r = −0.464, P = 0.0001).

Fig. 2

The correlation between serum IL-6 and age in 67 male and 67 female healthy subjects as revealed using the high sensitivity R&D assay. The individual values and regression lines are given. For clarity a value of 20.92 pg/ml, obtained for one female aged 60 years, has been omitted from the figure but is included in the linear regression and other statistical analyses presented. Note the highly significant positive correlation of IL-6 with age in males (r = 0.375, P = 0.0018) but not in females (r = 0.148, P = 0.231).

Fig. 3

The correlation between serum DHEA-S and IL-6 (R&D assay) in 67 male and 67 female healthy subjects. The individual values and regression lines are given. Note the significant negative correlation of IL-6 with DHEA-S in males (r = −0.242, P = 0.048) but not in females (r = 0.007, P = 0.955).

Fig. 4

The correlation between serum IL-6 sR and age and TGF-β1 and age in 38 male and 38 female healthy subjects. The individual values (□, males; ○, females) and regression lines are given. Note that IL-6 sR was not significantly correlated with age (r = 0.155, P = 0.182) and neither was TGF-β1 (r = 0.010, P = 0.931).