Endocrine Abstracts (2003) 6 P26

The relationship between serum levels of testosterone and inflammatory cytokines in men wih coronary artery disease

JE Nettleship1, RD Jones1, PJ Pugh2, KS Channer2 & TH Jones1,3

1Academic Unit of Endocrinology, The University of Sheffield, Sheffield, UK; 2Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK; 3Centre for Diabetes & Endocrinology, Barnsley District General Hospital, Barnsley, UK.

Evidence supports a protective role for testosterone in men with coronary artery disease (CAD) and in the regulation of cytokine function. This study examined the relationship between serum levels of inflammatory cytokines and testosterone in men with CAD. Serum was collected from 69 men (59+1 years) having >75% occlusion of 1 (n=20), 2 (n=18) or 3 (n=31) coronary arteries. Levels of total testosterone (TT), bioavailable testosterone (BT), tumour necrosis factor-alpha (TNFa), interleukin-1-beta (IL-1b), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured and analysis made between men with 1, 2 or 3 vessel CAD, and between hypogonadal (TT < 7.5nmol/L and/or BT < 2.5nmol/L) (n=17), borderline hypogonadal (12.0nmol/L > TT > 7.5nmol/L and/or 4.0nmol/L > BT > 2.5nmol/L) (n=22) and eugonadal (TT > 12.0nmol/L and/or BT > 4.0nmol/L) (n=30) men. In patients with 1, 2 or 3 vessel CAD, significant step-wise increases were observed in serum levels of IL-1b: 0.16+0.03, 0.22+0.06 and 0.41+0.08 pg/ml (P=0.035), and IL-10: 0.93+0.11, 1.17+0.14 and 2.94+0.65 pg/ml (P=0.008). No differences were seen in serum TNFa or IL-6. A significant stepwise increase in serum levels of IL-1b was also observed in eugonadal, borderline hypogonadal and hypogonadal men: 0.19+0.05, 0.29+0.05 and 0.46+0.13 pg/ml (P=0.047), and a weak inverse association was observed between serum BT and IL-1b: rp=-0.21 (P=0.083). Serum levels of IL-10 were not linked to serum testosterone, but were weakly correlated to serum levels of IL-1b: rp=0.21 (P=0.089). This data suggests that serum levels of IL-1b and IL-10 rise in accordance with disease extent in men with CAD. Serum levels of IL-1b and testosterone appear to be linked, suggesting endogenous testosterone may suppress production of this pro-inflammatory cytokine, or that IL-1b may lower testosterone synthesis/release. Elevated serum levels of anti-inflammatory IL-10 would appear to be a consequence of raised serum levels of IL-1b, rather than reduced serum testosterone.

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