interleukin-8 and Sexually-Transmitted-Diseases

Opportunistic infections (OIs) are common among human immunodeficiency virus (HIV) patients; however, genetic susceptibility to these infections has not been studied. Recent studies have shown that interleukin-8 (IL-8) A/T genotype carriers are more susceptible to a variety of diseases. In this study, we showed the effects of IL-8 gene polymorphisms on OIs and symptoms such as sexually transmitted diseases (STDs), tuberculosis (TB), diarrhea, shortness of breath, weight loss, and viral load, in HIV and acquired immunodeficiency syndrome patients. Genomic DNA was purified from mouthwash samples collected from patients attending HIV centers in the Vhembe district. The IL-8 (-251) A/T locus was genotyped using allele-specific polymerase chain reaction followed by agarose gel electrophoresis. The results showed a weak association between the IL-8 AA genotype and OIs such as STDs (P = 0.143), diarrhea (P = 0.906), and TB (P = 0.762). Significant associations were found between the IL-8 AT genotype and weight loss (P = 0.019), shortness of breath (P = 0.043), and skin problems (P = 0.003). Low viral load was also found to be significantly associated with IL-8 AA genotype (P = 0.009). The present study suggests that different IL-8 genotypes are associated with resistance to various OIs. However, further studies using larger samples sizes are needed to confirm this hypothesis.

Topics: Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Diarrhea; Female; Genetic Predisposition to Disease; Humans; Interleukin-8; Male; Middle Aged; Polymorphism, Single Nucleotide; Sexually Transmitted Diseases; South Africa; Tuberculosis; Viral Load; Young Adult

Women in Africa, especially young women, have very high human immunodeficiency virus (HIV) incidence rates that cannot be fully explained by behavioral risks. We investigated whether genital inflammation influenced HIV acquisition in this group.. Twelve selected cytokines, including 9 inflammatory cytokines and chemokines (interleukin [IL]-1α, IL-1β, IL-6, tumor necrosis factor-α, IL-8, interferon-γ inducible protein-10 [IP-10], monocyte chemoattractant protein-1, macrophage inflammatory protein [MIP]-1α, MIP-1β), hematopoietic IL-7, and granulocyte macrophage colony-stimulating factor, and regulatory IL-10 were measured prior to HIV infection in cervicovaginal lavages from 58 HIV seroconverters and 58 matched uninfected controls and in plasma from a subset of 107 of these women from the Centre for the AIDS Programme of Research in South Africa 004 tenofovir gel trial.. HIV seroconversion was associated with raised genital inflammatory cytokines (including chemokines MIP-1α, MIP-1β, and IP-10). The risk of HIV acquisition was significantly higher in women with evidence of genital inflammation, defined by at least 5 of 9 inflammatory cytokines being raised (odds ratio, 3.2; 95% confidence interval, 1.3-7.9; P = .014). Genital cytokine concentrations were persistently raised (for about 1 year before infection), with no readily identifiable cause despite extensive investigation of several potential factors, including sexually transmitted infections and systemic cytokines.. Elevated genital concentrations of HIV target cell-recruiting chemokines and a genital inflammatory profile contributes to the high risk of HIV acquisition in these African women.

Topics: Africa; Cervix Uteri; Chemokine CCL2; Chemokines; Cytokines; Disease Susceptibility; Female; Genital Diseases, Female; Genitalia, Female; HIV Infections; Humans; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-6; Interleukin-8; Sexually Transmitted Diseases; South Africa; Tumor Necrosis Factor-alpha; Uterine Cervicitis; Vagina; Vaginal Douching; Vaginitis; Young Adult

Bacterial vaginosis increases the susceptibility to sexually transmitted infections and negatively affects women's reproductive health.. To investigate host-vaginal microbiota interactions and the impact on immune barrier function, we colonized 3-dimensional (3-D) human vaginal epithelial cells with 2 predominant species of vaginal microbiota (Lactobacillus iners and Lactobacillus crispatus) or 2 prevalent bacteria associated with bacterial vaginosis (Atopobium vaginae and Prevotella bivia).. Colonization of 3-D vaginal epithelial cell aggregates with vaginal microbiota was observed with direct attachment to host cell surface with no cytotoxicity. A. vaginae infection yielded increased expression membrane-associated mucins and evoked a robust proinflammatory, immune response in 3-D vaginal epithelial cells (ie, expression of CCL20, hBD-2, interleukin 1β, interleukin 6, interleukin 8, and tumor necrosis factor α) that can negatively affect barrier function. However, P. bivia and L. crispatus did not significantly upregulate pattern-recognition receptor-signaling, mucin expression, antimicrobial peptides/defensins, or proinflammatory cytokines in 3-D vaginal epithelial cell aggregates. Notably, L. iners induced pattern-recognition receptor-signaling activity, but no change was observed in mucin expression or secretion of interleukin 6 and interleukin 8.. We identified unique species-specific immune signatures from vaginal epithelial cells elicited by colonization with commensal and bacterial vaginosis-associated bacteria. A. vaginae elicited a signature that is consistent with significant disruption of immune barrier properties, potentially resulting in enhanced susceptibility to sexually transmitted infections during bacterial vaginosis.

Topics: Actinobacteria; Antimicrobial Cationic Peptides; Epithelial Cells; Epithelium; Female; Humans; Immunity, Innate; Interleukin-1beta; Interleukin-6; Interleukin-8; Lactobacillus; Microbiota; Mucins; Prevotella; Sexually Transmitted Diseases; Species Specificity; Vagina; Vaginosis, Bacterial

To better understand innate immune responses to sexually-transmitted infection (STI) and the appropriateness of epithelial cell (EC) models of the vaginal and cervical mucosa, quantified toll-like receptor (TLR) expression from a population of women is needed.. TLR gene expression was quantified in primary and immortalized endocervical, ectocervical, and vaginal EC from multiple donors. TLR bioactivity was evaluated by cytokine elaboration.. TLR1-3 and 5-9 were expressed in each EC type with TLR2, 3, 5, 6 and CD14 expressed most abundantly. TLR4 was expressed by endocervical and vaginal EC. Agonist stimulation of TLR2, 3, 5 and 6 elicited cytokines. TLR4 and 7-9 were minimally expressed and were not consistently bioactive. Immortalized EC generally modeled primary cultures but elaborated significantly reduced cytokine levels.. TLR expression patterns were remarkably conserved across the study population and evaluated tissues indicating a predictable responsiveness to STI. The results support cautious use of immortalized cells for genital tract modeling.

Topics: Adult; Cervix Uteri; Chemokine CCL2; Cyclopropanes; Diglycerides; Epithelium; Female; Flagellin; Gene Expression Profiling; Guanosine; Humans; Immunity, Innate; Immunity, Mucosal; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipopolysaccharides; Oligopeptides; RNA, Double-Stranded; Sexually Transmitted Diseases; Toll-Like Receptors; Vagina