Clinical and immunological parallels in patients with infertility and chronic endometritis before and after exogenous cytokine therapy

Objective. To identify clinical and immunological parallels in patients with infertility and chronic endometritis before and after exogenous cytokine therapy. Subjects and methods. A prospective study was conducted in 58 women, including those with chronic endometritis (a study group, n=43) and healthy women (a comparison group, n=15). Endometrial samples were obtained by aspiration biopsy on days 20 to 24 of the cycle. The number of pinopodes, steroid receptors, viral inclusions, and chronic inflammation markers (CD 138, CD20, CD8, CD4, CD56, and HLA-DRII) were estimated by an immunohistochemical assay. Reverse transcription and real-time PCR assays were used to study the gene expressions of TLR4, TLR2, HBD1, and TNFa; HNP1-3 concentrations were estimated by enzyme-linked immunosorbent assay. A 20-day cycle of cytokine therapy with Superlymph 25 U was performed. An endometrial aspiration biopsy was repeated after the end of therapy. Results. After 20 days, high-quality CD138 detection using membrane staining was observed in 39.5% of the samples. The frequency of positive staining for CD20 reduced by 1.4 times; the count of CD8 and NK cells did not change; the number of CD4 and HLA-DRII increased by 1.7and 1.5 times, respectively; that of pinopodes rose by 1.27 times; the epithelial and stromal expressions of estrogen receptors increased by 1.3 and 3.2 times, respectively; those of progesterone receptors rose by 3 and 2.7 times, respectively; the detection of Epstein-Barr virus declined by 2.18 times, the expression of the TLR2 gene reduced by 1.3 times; the gene expressions of TLR4, TNFa, HBD1, and HNP1-3 increased by 1.5-, 1.2-, 2.1-, and 1.6-fold, respectively. Spontaneous pregnancy occurred in 19 (44.2%) patients within 1 to 6 months after the end of therapy. An inverse correlation was found between the increased gene expression of innate immunity factors and the decreased detection of chronic endometritis markers (CD138, CD20) and intracellular Epstein-Barr virus inclusions. Conclusion. The given results may suggest that exogenous cytokine therapy can be effective in patients with chronic viral endometritis.

TLR2, TLR4, plasma cells, chronic endometritis, infertility, cytokine therapy, innate immunity, TLR2, TLR4, defensin, tumor necrosis factor, Epstein-Barr virus, pregnancy