Mucosal immunity in the female reproductive tract: Correlation of immunoglobulins, cytokines, and reproductive hormones in human cervical mucus around the time of ovulation
ABSTRACT Mucosal surfaces serve as the portal of entry for many viral, bacterial, and parasitic infections. Understanding the immunity at mucosal membranes is essential to enhancing protection and decreasing infections. To evaluate the humoral and cellular immunity in the female reproductive tract, 15 reproductive-age women with a history of regular, cyclic monthly menses were recruited for this study. The presence of immunoglobulins and cytokines in cervical mucus was correlated with the production of reproductive hormones in sera. Cervical mucus specimens were collected at each daily visit beginning on cycle day 8 and continuing for 5 days postovulation. Volunteers were monitored by daily urinary LH testing coupled with transvaginal ultrasonography to ascertain follicular collapse. The cervix was washed in sterile saline before aspirating the cervical mucus from the cervical canal. Collection volumes ranged between 50 and 800 microl and were considered to represent the total mucus produced. Estradiol displayed the characteristic biphasic pattern with a peak before ovulation and in the luteal phase. Both IgG (30 mg/dl) and IgA (15 mg/dl) had a biphasic pattern with peak immunoglobulin levels detected 1 day before the estradiol peak and increasing again just after ovulation. Peak interleukin 10 (40 pg/ml) levels corresponded precisely with estradiol peak levels just before ovulation. Peak interleukin 1beta (1.3 ng/ml) levels occurred approximately 1 day before the estradiol peak. No apparent pattern in interleukin 6 (150 pg/ml) could be ascertained. Our data suggest a correlation between the IgG and IgA immunoglobulin levels, interleukin 1beta and interleukin 10, in the female reproductive tract and estradiol levels in the circulation. The increase in immunoglobulins and cytokines occurs approximately 1 day before the peak estradiol production before ovulation. These data suggest a role for cytokines and hormones in the regulation of reproductive tract immunity.
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- "Ashcroft et al., 1997; Angele and Faist, 2000; Klein, 2000b; Johansson et al., 2001). Evidence also comes from healthy women, by the use of correlational studies over women's menstrual cycles (e.g. with IgG, IgA, interleukin 10 and 1b: Kutteh et al., 1998) and studies of synthetic E 2 administration via hormonal contraceptives. However, most research on immunity and T is conducted with males, and most research on immunity and E 2 is conducted with females. "
ABSTRACT: Empirical evidence from clinical, nonhuman animal, and in vitro studies point to links between immune function and gonadal steroids, including potential androgenic immunosuppression and estrogenic immunoenhancement. This study was designed to test links between steroids and one marker of mucosal humoral immunity-immunoglobulin A (IgA) in healthy individuals, to facilitate comparisons with other species and clinical populations, as there are few existing studies with healthy humans that also allow gender/sex investigations. Participants (86 women, 91 men) provided a saliva sample for measurement of testosterone (T), estradiol (E(2)), and IgA. Results showed that E(2) was significantly and positively correlated with IgA in women, and group analyses by E(2) quartile showed that this association was linear. No significant correlations or nonlinear associations were seen between T and IgA in men or women, or E(2) and IgA in men. Evidence from this study indicates that IgA and E(2) are significantly associated in healthy premenopausal women.American Journal of Human Biology 05/2010; 22(3):348-52. DOI:10.1002/ajhb.20997 · 1.93 Impact Factor
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- "Ovulation was monitored using urinary luteinizing hormone (LH) test kits (OvuQuick, Quidel, San Diego, CA) coupled with transvaginal ultrasonography to ascertain follicular collapse (Miller and Soules, 1996). All results presented were standardized based on the day of ovulation (Kutteh et al., 1998). Vaginal la6age was collected after flushing 2 ml of sterile PBS over the cervix and around the external cervical os with a sterile plastic transfer pipette (Amand Manufacturing, San Fernando, CA). "
ABSTRACT: The purpose of this study was to determine the efficacy of intestinal tract immunization in the induction of specific antibodies in human female genital tract secretions. Live attenuated typhoid vaccine Ty 21a was administered to three groups of healthy female volunteers, who were not using hormonal contraceptives. Group 1 included 15 women vaccinated orally. Group 2 included seven of the same women, who were vaccinated rectally 6 months later. Group 3 included 11 volunteers, who were vaccinated rectally. Salmonella-specific antibodies of IgG and IgA were measured in vaginal lavage and cervical mucus after oral or rectal primary vaccination. Salmonella-specific antibodies measured 1 month after rectal booster vaccination demonstrated significant increases in vaginal fluids and cervical mucus and were dominated by IgA. These results indicate that specific antibodies in the human female genital tract induced by primary vaccination can be enhanced by subsequent rectal administration of vaccines.Journal of Reproductive Immunology 10/2001; 52(1-2):61-75. DOI:10.1016/S0165-0378(01)00109-7 · 2.37 Impact Factor
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- "The presence and stimulatory effects of cytokines on the mucosal immune system have been reported in both rodents and humans (McGhee et al., 1989; Prabhala and Wira, 1991, 1995; Kutteh et al., 1998). The multiregulatory cytokines such as interleukin (IL)-1i, IL-6, and IL-10 function in the maturation of B lymphocytes to immunoglobulin producing plasma cells (Edwards et al., 1995). "
ABSTRACT: Mucosal immunity in the female reproductive tract is influenced by immunoglobulins (Igs), cytokines, and reproductive hormones. Previous studies of reproductive-aged women demonstrated that IgA and IgG increases in cervical mucus corresponded to elevated levels of IL-1beta which occurred 1 day before the peak of endogenous estradiol production prior to ovulation. We sought to determine the effect of exogenous hormones on reproductive tract immunity in women on oral contraceptive pills (OCPs) and to compare the results with respect to naturally cycling women. Twelve women of reproductive age who had negative cervical cultures, a normal pap smear, and agreed to abstain from sexual intercourse during the study initiated OCPs. Cervical mucus and vaginal washes were collected at six intervals (2-3 days apart) throughout the treatment cycle. Fifteen naturally cycling women had similar samples collected prior to, during, and subsequent to ovulation. Cervical mucus samples were assayed for IgA, IgG, IL-1beta, IL-6, and IL-10 by enzyme-linked immunosorbent assay (ELISA). IgA, IgG and IL-1beta levels in women on OCPs paralleled increasing levels of norethindrone. Mean values of IgA increased from a low of 14.4+/-3.1 to 41.1+/-9.4 mg/dl and decreased significantly after the cessation of the pills (P < 0.001). In naturally cycling women, the largest quantities of Igs were detected prior to ovulation. By comparison, mean values of IgA in the cervical mucus of women on OCPs (24.4 mg/dl) exceeded peak levels of IgA in the cervical mucus of naturally cycling women (14.6 mg/dl). IgA was the predominant Ig detected in cervical mucus of women on OCPs. Both immunoglobulins in each group exhibited changes relative to their hormonal status. The increased levels of IgA in the cervical mucus of women on OCPs may explain the clinical observation of a lower incidence of sexually transmitted diseases.Journal of Reproductive Immunology 04/1999; 42(2):93-106. DOI:10.1016/S0165-0378(98)00086-2 · 2.37 Impact Factor