Guthrie Brandon L, Introini Andrea, Roxby Alison C, Choi Robert Y, Bosire Rose, Lohman-Payne Barbara, Hirbod Taha, Farquhar Carey, Broliden Kristina
Departments of *Global Health; †Epidemiology, University of Washington, Seattle, WA; ‡Department of Medicine, Solna, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; §Department of Medicine, University of Washington, Seattle, WA; and ‖Center for Public Health Research, Kenya Medical Research Institute, Nairobi, Kenya.
J Acquir Immune Defic Syndr. 2015 May 1;69(1):1-10. doi: 10.1097/QAI.0000000000000533.
The effects of sex hormones on the immune defenses of the female genital mucosa and its susceptibility to infections are poorly understood. The injectable hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may increase the risk for HIV-1 acquisition. We assessed the local concentration in the female genital mucosa of cationic polypeptides with reported antiviral activity in relation to DMPA use.
HIV-1-uninfected women were recruited from among couples testing for HIV in Nairobi, Kenya. Cervicovaginal secretion samples were collected, and the concentrations of HNP1-3, LL-37, lactoferrin, HBD-2, and SLPI were measured by enzyme-linked immunosorbent assays. Levels of cationic polypeptides in cervicovaginal secretions were compared between women who were not using hormonal contraception and those using DMPA, oral, or implantable contraception.
Among 228 women, 165 (72%) reported not using hormonal contraception at enrollment, 41 (18%) used DMPA, 16 (7%) used an oral contraceptive, and 6 (3%) used a contraceptive implant. Compared with nonusers of hormonal contraception, DMPA users had significantly higher mean levels of HNP1-3 (2.38 vs. 2.04 log₁₀ ng/mL; P = 0.024), LL-37 (0.81 vs. 0.40 log10 ng/mL; P = 0.027), and lactoferrin (3.03 vs. 2.60 log₁₀ ng/mL; P = 0.002), whereas SLPI and HBD-2 were similar.
Although all analyzed cationic polypeptides have intrinsic antiviral capacity, their interaction and cumulative effect on female genital mucosa susceptibility to infections in vivo has yet to be unraveled. This study suggests a potential mechanism underlying the effect of DMPA on the innate immune defenses, providing a rationale to investigate its effect on HIV-1 acquisition risk.
性激素对女性生殖黏膜免疫防御及其感染易感性的影响尚不清楚。注射用激素避孕药醋酸甲羟孕酮长效避孕针(DMPA)可能会增加获得HIV-1的风险。我们评估了具有抗病毒活性的阳离子多肽在女性生殖黏膜中的局部浓度与DMPA使用情况的关系。
从肯尼亚内罗毕进行HIV检测的夫妇中招募未感染HIV-1的女性。收集宫颈阴道分泌物样本,通过酶联免疫吸附测定法测量HNP1-3、LL-37、乳铁蛋白、HBD-2和SLPI的浓度。比较未使用激素避孕的女性与使用DMPA、口服或植入式避孕的女性宫颈阴道分泌物中阳离子多肽的水平。
在228名女性中,165名(72%)报告在入组时未使用激素避孕,41名(18%)使用DMPA,16名(7%)使用口服避孕药,6名(3%)使用避孕植入物。与未使用激素避孕的女性相比,使用DMPA的女性HNP1-3的平均水平显著更高(2.38对2.04 log₁₀ ng/mL;P = 0.024),LL-37(0.81对0.40 log10 ng/mL;P = 0.027)和乳铁蛋白(3.03对2.60 log₁₀ ng/mL;P = 0.002),而SLPI和HBD-2相似。
尽管所有分析的阳离子多肽都具有内在的抗病毒能力,但它们在体内对女性生殖黏膜感染易感性的相互作用和累积效应尚未阐明。本研究提示了DMPA对先天免疫防御作用的潜在机制,为研究其对HIV-1获得风险的影响提供了理论依据。