Kaori Mitsukawa

Cervical inflammatory cytokines and other markers in the cervical mucus of pregnant women with lower genital tract infection

Objective: To evaluate concentrations of interleukin (IL)‐6, IL‐8, lactoferrin (LF), and alpha defencine (α‐DF) in the cervical mucus of pregnant women and analyze their relation to cervicitis and bacterial vaginosis (BV). Methods: Cervical mucus samples were obtained from August 2003 through May 2004 from 157 women who were between the 6th and 36th week of an uncomplicated singleton pregnancy. All women were delivered at term, 69 without BV or cervicitis, 9 with BV, and 79 with cervicitis. Results: Interleukin 8, LF, and μ‐DF concentrations were higher in women with cervicitis (0.81 ± 0.36 pg/mL, 14.8 ± 12.3 μg/mL, and 0.60 ± 0.49 μg/mL) than in women without BV or cervicitis (0.35 ± 0.34 pg/mL, 8.0 ± 11.0 μg/mL, and 0.15 ± 0.12 μg/mL). Interleukin 6 concentration was higher in women with BV (0.26 ± 0.32 pg/mL) than in women without BV or cervicitis (0.09 ± 0.15 pg/mL) or in women with cervicitis (0.12 ± 0.18 pg/mL). Conclusions: Higher levels of inflammatory cytokines in the cervical mucus of pregnant women may lead to early detection of lower genital tract infection.

Recombinant human lactoferrin inhibits matrix metalloproteinase (MMP-2, MMP-3, and MMP-9) activity in a rabbit preterm delivery model

Aim:  To investigate the effect of recombinant human lactoferrin (rh‐LF) on the expression of matrix metalloproteinase as a marker of cervical maturation, using a rabbit preterm delivery model in which preterm labor was induced by bacteria.

Concentration of lactoferrin and interleukin-6 in cervical mucus from patients being treated for infertility

BackgroundThe concentrations of the iron-binding protein lactoferrin (LF) and interleukin-6 (IL-6) were measured in the cervical mucus of patients being treated for infertility throughout the menstrual cycle.MethodsA total of 251 cervical mucus samples were obtained from the patients throughout the menstrual cycle. One hundred and fifty samples were from primary infertility patients with unexplained infertility and 101 samples were from secondary infertility patients as a control. The concentrations of LF and IL-6 were measured by enzyme immunoassays. The standard curve of LF concentrations ranged from 1.6 to 50 ng/mL.ResultsThe mean LF and IL-6 concentrations in the cervical mucus of primary infertility patients were higher than that of the control patients (P = 0.04,P = 0.032, respectively) The LF and IL-6 concentrations were highly correlated (P < 0.0001).ConclusionElevated levels of IL-6 and LF in the cervical mucus were obtained from primary infertility patients. We speculate that LF might also be one of the causes of infertility and might play an important role in reproductive processes in the cervix.

Concentration of lactoferrin and interleukin-6 in cervical mucus from patients being treated for infertility: Lactoferrin and IL-6 in cervical mucus

Background:  The concentrations of the iron‐binding protein lactoferrin (LF) and interleukin‐6 (IL‐6) were measured in the cervical mucus of patients being treated for infertility throughout the menstrual cycle.

Potential of Lactoferrin in the Prevention of Preterm Delivery

Summary Objective Chorioamnionitis (CAM), an ascending infection from maternal bacterial vaginosis or cervicitis, can cause preterm delivery. We hypothesized that lactoferrin (LF), in particular recombinant human LF (rh-LF), may prevent preterm delivery. We conducted three experiments to demonstrate LFs ability to prevent preterm delivery. Materials and Methods First, we correlated human cervical mucus LF concentration and LF and interleukin- 6 (IL-6) concentrations in amniotic fluid to gestational weeks, in mothers with and without CAM. Second, using an amnion cell culture system, we studied the preventive effect of rh-LF on inflammatory cytokine production induced by lipopolysaccharide. Using human cervical gland cell lines, we studied the preventive effects of rh-LF on the growth of Escherichia coli . Thirdly, we studied the preventive effect of rh-LF in mouse and rabbit models of preterm delivery. We also examined LFs preventive effect on the production of inflammatory cytokines in maternal serum and amniotic fluid. Results In mothers with CAM, amniotic fluid LF concentrations were elevated and IL-6 production increased as fetal LF levels and inflammation increased. LF administration prevented IL-6 production, demonstrating LFs anti-cytokine action and control over E. coli . Length of pregnancy was extended and fetal survival rates were higher in mothers who received LF. Conclusion It appears that LF is highly beneficial in the prevention of preterm delivery and improving poor fetal prognosis due to elevated inflammatory cytokine levels. Specifically, rh-LF may prevent the production of inflammatory cytokines under E. coli infection or control maternal cytokine production.