Cyclic Changes in the Level of the Innate Immune Molecule, Surfactant Protein‐A, and Cytokines in Vaginal Fluid

Abstract

PROBLEM Our knowledge of the innate host-defenses in the vagina, a site where these defenses are essential to protecting the host upper reproductive tract from invasion by pathogens, is as yet rudimentary. Specifically, little is known about the pattern-recognition component of vaginal innate immunity, the relationship of pattern-recognition molecules to known cytokine levels, and the role of gonadal hormones in their regulation. METHOD OF STUDY We measured levels of Surfactant Protein-A (SP-A), a prototypic innate pattern-recognition protein, in vaginal fluid (VF) and correlated them with levels of IL-1β and IL-8, two cytokines known to be present in VF. Assays were carried out on VF collected over three consecutive cycles from ten healthy naturally cycling women who were sampled at three specific time points in the menstrual cycle. The three time points were chosen to enable correlation with distinct hormonal states. RESULTS Both SP-A and cytokines levels were highest 5–6 days after menses (p < 0.05) and were significantly lower at ovulation and mid-luteal phase. CONCLUSION SP-A, like other host-defense molecules in the reproductive tract, appears to be regulated by gonadal hormones.

Reduced levels of genital tract immune biomarkers in postmenopausal women: implications for HIV acquisition

“…Several other studies have described altered levels of immune mediators through stages of the cycle [51,52,56,57]. One explanation for variable findings across studies might be that cycle length in women are different, and samples might not have been collected at exactly the same time of the cycle in different studies.…”

Innate Immunity in the Vagina (Part II): Anti-HIV Activity and Antiviral Content of Human Vaginal Secretions

“…The absence of consistent mid-cycle decreases in HBD2, elafin and the other cytokines suggests that VEC, despite their ability to produce antimicrobials, are not exclusive or major contributors to the mid-cycle decline observed elsewhere 23 . Unfortunately, previous publications provide a complicated backdrop against which to make comparisons, and it is still unclear whether a mid-cycle drop in cytokine, chemokine or antimicrobial levels occurs in vivo 23, 32, 33 . For example, Keller et al (2007) demonstrated that antimicrobials, cytokines and chemokines including SLPI, HBD2, IL-8 and lactoferrin decrease at mid-cycle in CVL recovered from healthy premenopausal women while total protein concentration remains relatively constant 23 .…”

The role of sex hormones in immune protection of the female reproductive tract

“…Contained within the fluid are various immunomodulatory molecules including cytokines, chemokines, antimicrobial proteins, enzymes and growth factors. In cervico-vaginal lavage fluid (CVL fluid), the concentrations of antimicrobial proteins such as SLPI, HBD2, human neutrophil peptide 1 (HNP1; also known as neutrophil defensin 1), HNP2, HNP3, lysozyme, lactoferrin and surfactant A markedly decrease by mid-cycle (day 13) and remain low for 7–10 days during the secretory phase before returning to the higher levels found during the proliferative phase following menstruation 26,27 . These findings suggest that the antimicrobial contribution of the luminal fluid to overall immune protection in the FRT decreases during the secretory phase.…”