Enhanced immunological response by dendritic cells in male hypogonadism
Corrales JJ, Almeida M, Cordero M, Martín-Martín L, Méndez C, Miralles JM, Orfao A.

Source Eur J Clin Invest. 2012 Jul 27. doi: 10.1111/j.1365-2362.2012.02712.x. [Epub ahead of print]

Service of Endocrinology, University Hospital of Salamanca, Salamanca, Spain Department of Medicine, University of Salamanca, Salamanca, Spain Service of Flow Cytometry, University of Salamanca, Salamanca, Spain.Abstract Eur J Clin Invest 2012;

ABSTRACT: Background  The effect of male hypogonadism on the immune response is poorly understood, even though testosterone has both immunosuppressive and anti-inflammatory effects in men. Design  In this study, we compared the distribution and functional status of peripheral blood (PB) monocytes, dendritic cells (DCs) [CD16(+) (monocytoid), CD33(+) (myeloid) and CD33(-) (plasmacytoid)] and CD4(+)  CD25(+)  CD127(-/lo) regulatory T cells from hypogonadic men and control subjects. Immunophenotypic studies were performed both on resting and in vitro-stimulated cells. Results  Overall, no significant differences were detected on the number of monocytes, DCs and CD4(+ ) CD25(+ ) CD127(-/lo) regulatory T cells between both groups of subjects. However, hypogonadic men showed slightly higher numbers of circulating CD16(+) cells expressing the CD107b activation/degranulation-associated marker than controls, such differences reaching statistical significance after in vitro stimulation with CpG oligodeoxynucleotides. Interestingly, antigen-stimulated expression of CD107b on CD16(+) cells inversely correlated with the serum concentrations of total testosterone (r(2)  = -0•45; P = 0•01), free testosterone (r(2)  = -0•48; P = 0•005), calculated free testosterone (r(2)  = -0•44; P = 0•01) and bioavailable testosterone (r(2)  = -0•46; P = 0•008) among all cases studied, as well as with both the LH (r(2)  = -0•53, P = 0•04) and FSH (r(2)  = -0•54, P = 0•04) serum levels among hypogonadic men. Conclusions  These findings show an enhanced immunological response of circulating (activated) CD16(+) DCs to antigen stimulation, which was inversely related to testosterone and gonadotropin serum levels. Such findings suggest a modulation by the hypothalamic-hypophyseal-gonadal axis of the immune response and may have clinical implications for hypogonadic men, as regards susceptibility to autoimmune diseases and increased responses to antigenic stimuli.