Influência da 5 alfa- dihidrotestosterona sobre a resposta de macrófagos peritoneais murinos e monócitos humanos induzida por Staphylococcus aureus

Abstract

Introduction: Staphylococcus aureus (S. aureus) infections have a high morbidity and mortality rate, considered a major problem for public health, with males being more affected by these infections. There is little information in the literature on the role of testosterone in infections caused by S. aureus. Objective: To evaluate the influence of 5α-dihydrotestosterone (DHT) on the response of murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (hPMs) in the immune response induced by S. aureus. Methodology: An in vitro model of MPMs was carried out from male BALB/C mice, with sham surgery (Shams), orchiectomized (OQX) and from females and hPMs of young men and women of childbearing age, healthy, with steroid levels within the normal range. Cells were inoculated with S. aureus or sterile saline (control). Cytokines TNF-α, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12, GM-CSF, total nitrites and hydrogen peroxide (H2O2) were measured in culture supernatant. in MPMs and in hPMs. Furthermore, by RT-PCR array, the analysis of 84 genes involved in the immune response against S. aureus was performed. Results: In MPMs, cells inoculated with S. aureus from Sham males showed higher levels of inflammatory cytokines (TNF-α, IL-1α, IL-8) and lower concentrations of IL-10, total nitrites and H2O2 compared to OQX. In relation to females, cells from Sham males inoculated with S. aureus also showed higher concentrations of pro-inflammatory cytokines (TNF-α, IL-1α, IL-6, IL-8) and lower concentrations of IL-10 and nitrites totals and H2O2. In the treatment with DHT, the concentration of inflammatory cytokines and the expression of genes such as toll-like receptor 2 (TLR2) and nuclear factor kappa B (NF-kB) were higher in OQX treated with the hormone compared to OQX without pre-treatment. In addition, the concentrations of total nitrites and H2O2 were lower in pre-treatment cells, both in OQX male and female cells. For the human experiment, hPMs from men inoculated with S. aureus had higher concentrations of inflammatory cytokines (TNF-α, IL-6, IL-12, GM-CSF) and lower concentrations of IL-1β and IL-10 , total nitrites, and H2O2 compared to women's hPMs. In response to treatment with DHT, the hormone inhibited the concentrations of total nitrites, H2O2 and increased the expression of TLR2 and genes involved in the NF-kB pathway in MPMs and hPMs. Conclusion: Our results demonstrate that there is a difference between the sexes in the response to inoculation by S. aureus, females have a better immune defense response against this pathogen and DHT has pro-inflammatory immunomodulatory properties in MPMs and in hPMs. It is hoped that a better understanding of the role of testosterone in the body's defense response against microorganisms can propose strategies for an effective, safe and useful treatment. In addition, it can contribute to actions to promote the health of the population, resulting in the reduction of costs with treatments and hospitalizations.