The clinical role of interleukin-6 and interleukin-6 soluble receptor in human follicular fluids

Abstract

In order to investigate the role of interleukin-6 (IL-6) and interleukin-6 soluble receptor (sR) in human ovulation, we evaluated the concentrations in human follicular fluid and analyzed the correlation of IL-6 and IL-6 sR with oocyte maturation. The oocytes were obtained from the follicular fluid of 45 women undergoing in vitro fertilization and embryo transfer. The concentrations of IL-6 and IL-6 sR in follicular fluid were measured by ELISA. In addition, granulosa cells obtained from the follicular fluid were cultured and treated with forskolin and 12- o-tetradecanoylphorbol 13-acetate for 24-48 h. The concentration of IL-6 was significantly higher in the follicular fluid than in the serum (P<0.01). In contrast, the concentration of IL-6 sR was significantly lower in the follicular fluid than in the serum (P<0.001). The concentrations of IL-6 and IL-6 sR were significantly higher in the follicular fluid containing mature oocytes than in fluid containing immature oocytes (P<0.05). The production of IL-6 was markedly increased over the basal level after 24 h of treatment with forskolin (P<0.001) and 48 h of treatment (P<0.01) with cultured granulosa cells. Our data suggest that IL-6 and IL-6 sR may play an important role in follicular growth and development in human preovulatory processes. It is possible that IL-6 in particular may be regulated by cAMP. IL-6 and IL-6 sR might also be valuable biochemical markers in the evaluation of oocyte maturation.

Low follicular fluid IL-6 levels in IVF patients are associated with increased likelihood of clinical pregnancy

“…FF levels of IL-6 were unrelated to COH protocol or fertilization rates and in this context our findings are consistent with published data [33,34]. Given our study design where FF samples were pooled for each patient, we cannot relate FF IL-6 with individual oocytes within each follicle; the linear relationship observed between FF IL-6 and yield of mature oocytes however, is supportive of previously published work by Kawasaki et al [25]; these authors described higher IL-6 levels in fluid from follicles yielding mature oocytes. Our data identify adverse influences of an intrafollicular inflammatory milieu on successful CP following fresh embryo transfer; given the lack of observed detriment on parameters of COH nor on fertilization, endometrial receptivity may be identified as a likely target for deleterious influences of elevated FF IL-6 levels, as suggested by the observed decline in rates of CP and implantation with increasing FF IL-6 levels.…”

“…Measurements of serum and follicular fluid (FF) levels of IL-6 in women undergoing in vitro fertilization (IVF) have been shown previously to be associated with etiology of infertility, stimulation protocol, fertilization rates and pregnancy outcome [7,[23][24][25][26], and increased FF levels of IL-6 are described in the context of ovarian hyperstimulation syndrome [27].…”

Changes in Expression of Interleukin-6 Receptors in Granulosa Cells During Follicular Atresia in Pig Ovaries

“…In the present study, we investigated the changes in the expression of IL-6 receptors (IL-6Rα, IL-6sR and gp130) in granulosa cells and follicular fluid during atresia. The expressions of IL-6Rα and gp130 in human and rat granulosa cells [33,35] and IL-6sR in human follicular fluid [36] have previously been reported. We detected the expressions of IL-6Rα and gp130 in granulosa cells and IL-6sR in follicular fluid from the porcine ovary.…”

Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis

“…Presently, there is accumulating evidence suggesting that individual cytokines in human follicular fluid can be used as predictors of IVF outcome [30]. A positive association of IL-6 with oocyte maturation [31] and IL-1β with embryo development and pregnancy [32] is documented. A majority of findings have indicated that IL-12 is negatively associated with folliculogenesis, oocyte quality, and implantation [30,33,34].…”