TESTOSTERONE FAVORS A HIGHER RECRUITMENT OF NEUTROPHILS WITH REDUCED EFFICIENCY IN KILLING BACTERIA

SCALERANDI MV; LEIMGRUBER C; PEINETTI N; NICOLA JP; MALDONADO CA; QUINTAR AA

Congreso; LXI Sociedad Argentina de Investigación Clínica (SAIC). LXIV Sociedad Argentina de Inmunología (SAI). XLVIII Sociedad Argentina de Farmacología Experimental (SAFE); 2016

Although androgens have been suggested to exertmodulatory functions on adaptive immunity, there is scarceevidence about their role on the innate immune/inflammatoryresponse. Considering that neutrophils are essential effector cells against bacterial pathogens, the aim of this work was to evaluate the effects of testosterone on neutrophils infiltrating the prostate gland. Adult maleWistar rats were first orchiectomized and immediately replaced with testosterone at physiological level (T) or vehicle (OX), and then subjected to acute prostatitis by intra-prostatic inoculation of E. coli (for 5 days, T+BP andOX+BP groups) or LPS (for 24 hs, T+LPS and OX+LPS groups). T+BP animals showed a higher neutrophil infiltration compared to OX+BP, with intense E. coli immunostaining,correlating with the presence of phagocytosedbacteria in active neutrophils by electron microscopy. In LPS-induced prostatitis, testosterone treatment also promoted a higher neutrophil recruitment (Gr+) cells per gland by flow cytometry, which was correlated to anincreased mRNA expression of CXCL1 and CXCL2), with the cells having a lower myeloperoxidase (MPO) activity. Interestingly, sorted Gr+ infiltrating neutrophils showed a higher mRNA expression of IL10 and IL6 in T+LPS byqPCR. Finally, testosterone also increased thioglycollate induced neutrophil recruitment in the peritoneum, with the cells exhibiting a reduced bactericidal ability when coincubating ex vivo with E. coli. These findings reveala intriguing role for testosterone on the early inflammatory response in the prostate, with neutrophils being a main target. Testosterone increases local chemokine expression, leading to a higher recruitment of neutrophilsto the site of infection. However, testosterone favors an IL10 high MPO low phenotype, with reduced efficiency in killing bacteria. This immunomodulatory effect of testosterone represents a novel factor to consider in alternativeapproches for inflammatory diseases.