Endocrine Abstracts (2002) 3 P252

Testosterone increases interleukin 10, an anti-inflammatory cytokine, in whole blood from hypogonadal men

GL Corlett1, PJ Pugh1,3, D Kapoor2, RD Jones1, KS Channer1,3 & TH Jones1,2

1Endocrine Heart and Pituitary Group, Academic Unit of Endocrinology, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, UK; 2Centre for Diabetes and Endocrinology, Barnsley District General Hospital, Bransley, UK; 3Department of Cardiology, Royal Hallamshire Hospital, Sheffield, UK.

Background: Testosterone has been shown to have anti-inflammatory properties and may suppress production of pro-inflammatory cytokines. In this study, we examined the effects of testosterone on the ex-vivo production of the anti-inflammatory cytokine interleukin- (Il-)10 in whole blood from hypogonadal men.

Method: 16 men with new diagnosis of hypogondism were studied. Mean age was 61.7 (2.9) years, plasma total testosterone was 6.4 (0.4) nM. Blood was collected between 0800 and 0900 into five containers, which also contained an equal volume of phosphate buffer solution and heparin at a concentration of 10IU/ml. The samples where then incubated at 37degC alone, with testosterone at concentrations of 10nM, 1 micromolar or 100 micromolar or with the cyclodextrin vehicle as a control. After an hour incubation, lipopolysaccharide (LPS) at a concentration of 1 microgram per ml was added to each sample and incubation continued for 3 hours. Samples where then spun at 3000rpm for 15 minutes and the supernatant collected and stored at -80degC for later analysis. Measurement of Il-10 was carried out by means of Diaclone commercial ELISA kits.

Results (as mean (SEM)): Addition of LPS to the samples resulted in production of Il-10, which was not significantly altered by the cyclodextrin vehicle (18.4 (3.9) pg/ml v 21.2 (4.4) pg/ml, p=0.30). Samples incubated with testosterone showed a significant increase in Il-10 production (43.8 (10.6) pg/ml at 10nM, p=0.01; 28.5 (4.2) pg/ml at 1 micromolar, p= 0.03; 33.2 (5.7) pg/ml at 100 micromolar, p=0.02), which did not appear to be dose dependent.

Conclusion: In men with hypogonadism, testosterone increases the production of the anti-inflammatory cytokine Il-10 by LPS-stimulated whole blood in vitro. This may have clinical relevance both to hypogonadal men and to patients with inflammatory diseases such as arthritis and coronary artery disease.

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