目的:炎症介质是免疫应答的重要调节因子,可以调节病毒感染引起的炎症反应。包括人乳头瘤病毒(HPV)。在这项研究中,我们评估了宫颈免疫介质之间的关联,包括趋化因子,细胞因子,和HPV感染的生长因子。
方法:我们使用基于非磁性珠的多重检测方法,在前瞻性纵向队列设计中,从275名女性的宫颈分泌物中确定了27种免疫介质。所有研究参与者年龄在18岁或以上,有阴道性交史,目前没有怀孕,无宫颈疾病或子宫切除术史。
结果:参与者的平均(±标准差)年龄为41(±8)岁,约一半(51%[141/275])为HPV阳性,其中7%(10/141)患有低危HPV(lrHPV),61%(86/141)有高危型HPV(hrHPV),32%(45/141)同时感染lrHPV和hrHPV。较高浓度的一些免疫介质与HPV感染有关。包括eotaxin,干扰素-γ,白细胞介素(IL)-1β,IL-2、IL-4、IL-7、IL-8、IL-9、IL-10、IL-12p70、IL-13、IL-15、巨噬细胞炎性蛋白(MIP)-1α、MIP-1β,在激活正常T细胞表达和分泌(RANTES)时受到调节,和肿瘤坏死因子(TNF)-α和任何HPV;IL-2,IL-4,IL-5,IL-7,IL-10,IL-12p70和IL-13和lrHPV;和eotaxin,干扰素,IL-1B,IL-4、IL-7、IL-8、IL-9、IL-10、IL-13、IL-15、MIP-1α、MIP-1β,RANTES,TNF-α浓度,和hrHPV感染。较高浓度的粒细胞巨噬细胞集落刺激因子,IL-1受体拮抗剂(IL-1Ra),单核细胞趋化蛋白-1(MCP-1)与任何HPV的几率降低相关,而IL-1Ra和MCP-1与hrHPV感染几率降低相关。
结论:几种趋化因子,细胞因子,在这一女性人群中,生长因子与群体特异性HPV感染相关.这些重要的发现有助于了解HPV的免疫反应,细胞因子谱及其对宫颈发病机制的潜在影响,并可以指导该领域未来的研究。
OBJECTIVE: Inflammatory mediators are important regulators of immune response and can modulate the inflammation caused by viral infections, including human papillomavirus (HPV). In this study, we evaluated the association between cervical immune mediators, including chemokines, cytokines, and growth factors with HPV infections.
METHODS: We used a nonmagnetic bead-based multiplex assay to determine 27 immune mediators in cervical secretions collected from 275 women in a prospective longitudinal cohort design. All the study participants were age 18 years or older, had a history of vaginal sexual intercourse, were not currently pregnant, and had no history of cervical disease or hysterectomy.
RESULTS: The mean (±standard deviation) age of the participants was 41 (±8) years, and about half (51% [141/275]) were HPV-positive, of whom 7% (10/141) had low-risk HPV (lrHPV), 61% (86/141) had high-risk HPV (hrHPV), and 32% (45/141) had both lrHPV and hrHPV infections. Higher concentrations of some immune mediators were associated with HPV infections, including eotaxin, interferon-gamma, interleukin (IL)-1β, IL-2, IL-4, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, macrophage inflammatory protein (MIP)-1α, MIP-1β, regulated upon activation normal T-cell expressed and secreted (RANTES), and tumor necrosis factor (TNF)-α and any HPV; IL-2, IL-4, IL-5, IL-7, IL-10, IL-12p70, and IL-13 and lrHPV; and eotaxin, interferon, IL-1B, IL-4, IL-7, IL-8, IL-9, IL-10, IL-13, IL-15, MIP-1α, MIP-1β, RANTES, TNF-α concentrations, and hrHPV infections. Higher concentrations of granulocyte macrophage colony-stimulating factor, IL-1 receptor antagonist (IL-1Ra), and monocyte chemotactic protein-1 (MCP-1) were associated with reduced odds of any HPV, while IL-1Ra and MCP-1 were associated with reduced odds of hrHPV infections.
CONCLUSIONS: Several chemokines, cytokines, and growth factors are associated with group-specific HPV infections in this population of women. These important findings contribute to the understanding of the immune response to HPV, cytokine profiles and their potential implications for cervical pathogenesis, and can guide future research in this field.