UMLS:C0021359 - FACTA Search

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Query: UMLS:C0021359 (infertility)
26,075 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chlamydia trachomatis infects the upper genital tract of millions of women, causing infertility and pelvic inflammatory disease, yet the inflammatory response to C. trachomatis infection is poorly understood. The cytokine response and the phenotype of infiltrating lymphocytes during C trachomatis infection of fimbria and ampulla autografts in subcutaneous pockets in Macaca nemestrina were characterized. About two-thirds of the infiltrating lymphocytes were CD8 T cells, with the remainder being CD4 T cells and B cells. Interleukin (IL)-2, IL-6, IL-10, interferon-gamma (IFN-gamma), and perforin mRNA were produced by the infiltrating cells, but IL-4 mRNA was absent. The presence of CD8 T cells and perforin mRNA suggest that activated cytolytic T cells are present. The presence of IL-2 and IFN-gamma mRNA and the absence of IL-4 mRNA suggest that Th1-type cytokines predominate during the acute phase of C. trachomatis infection of the upper genital tract.
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PMID:Analysis of lymphocyte phenotype and cytokine activity in the inflammatory infiltrates of the upper genital tract of female macaques infected with Chlamydia trachomatis. 876 30

Chlamydia trachomatis-associated female infertility and ectopic pregnancy are caused by postinflammatory fibrosis and scarring of the upper genital tract. Scarring of the upper genital tract is associated with multiple infectious episodes with C. trachomatis. To study the immune response that occurs with multiple infections of C. trachomatis in the female upper genital tract, a Macaca nemestrina model was used. Subcutaneous pockets containing autologous salpingeal tissue implants were inoculated three times with C. trachomatis. The inflammation after three inoculations was associated with a mononuclear infiltrate dominated by CD8 T-cell lymphocytes. Perforin mRNA was induced in infected pockets, demonstrating that activated cytolytic lymphocytes were present in the lesions. Fibrosis, as evidenced by fibroblast proliferation and connective tissue deposition, was observed by the third infection. Cytokine mRNAs induced by repeated chlamydial infection included gamma interferon, interleukin-2 (IL-2), IL-6, and IL-10 mRNAs, but IL-4 mRNA was not induced. Nearly identical findings were found in macaque fallopian tubes infected in situ repeatedly with C. trachomatis, validating the subcutaneous pocket model of chlamydial salpingitis. However, it was not possible to evaluate if there was an induction of perforin mRNA in infected salpingeal tubes in situ, because there was a high basal level of perforin mRNA in these tissues. These results suggest that repeated chlamydial infection of the female upper genital tract leads to CD8 T-cell predominance, a Th1-like cytokine milieu, and these inflammatory changes are associated with progression to fibrosis associated with female infertility.
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PMID:Repeated Chlamydia trachomatis infection of Macaca nemestrina fallopian tubes produces a Th1-like cytokine response associated with fibrosis and scarring. 916 48

The cytokines are (glyco)proteins secreted by lymphoid and non-lymphoid cells which modulate several biological responses including the ovarian function. Interleukin (IL)-1 and tumour necrosis factor (TNF)-alpha suppress 17beta-estradiol (E2) and progesterone release from granulosa and luteal cells in vitro. TNF-alpha affects negatively folliculogenesis and ovarian maturation. Additional in vivo evidence for a role of this macrophage-derived cytokine came from our recent observation that women with infertility due to immunological causes have elevated intrafollicular fluid levels of TNF-alpha and decreased levels of E2 compared to women with a tubal factor of infertility. Because the macrophages are a primary component of the intrafollicular compartment, the present study was undertaken to evaluate whether other macrophage-derived cytokines are also released in the human follicular fluid. To accomplish this, we measured the levels of IL-1beta, IL-6, IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the follicular fluids of two groups of infertile women undergoing to an in vitro fertilization program. The first group of women had a significant titre of anti-spermatozoon antibodies in the serum and/or the mucus as the only cause of infertility, whilst the second group of women was infertile because of non patent fallopian tubes. Intrafollicular cytokines levels were measured by solid-phase ELISA and steroid concentrations by radioimmunoassay. Whilst IL-1beta, IL-6, IL-10, and GLM-CSF were all measurable in the follicular fluid of both groups of women, the levels of IL-6 were found to be significantly more elevated and those of GM-CSF lower in patients with infertility due to immunological causes as compared to those with tubal infertility. The former had also decreased intrafollicular E2 levels and increased progesterone concentrations. No difference was seen in the follicular fluid levels of testosterone and androstenedione. In conclusion, several macrophage-derived cytokines are present in the follicular fluids of infertile women. Patients with infertility due to immunological causes had higher levels of IL-6 and lower concentrations of GM-CSF as compared to patient with a tubal factor of infertility. We speculate that this abnormal cytokine profile may contribute to the altered intrafollicular steroid milieu.
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PMID:Macrophage-derived cytokines in the follicular fluids of women with infertility due to immunological causes. Elevated levels of interleukin 6 and low levels of granulocyte-macrophage colony-stimulating factor. 981 36

Peripheral lymphocytes in uninfected fertile controls, women with various histories of Chlamydia trachomatis infection, pelvic inflammatory disease (PID) and infertility not due to C. trachomatis infection (endometriosis) were cultured overnight with PHA mitogen and the 60 kDa chlamydial heat shock protein. Plasma samples were then assayed for levels of gamma-interferon and IL-10 using a commercial ELISA system. Women with PID and those with a history of multiple C. trachomatis infections showed reduced gamma-interferon production in response to cHSP60, not seen in women infected only once and those with infertility due to other causes (endometriosis). Secretion of IL-10 in response to cHSP60 did not vary significantly across the various patient groups, though all patients showed elevated levels of total IL-10 compared with uninfected controls.
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PMID:Reduced levels of gamma-interferon secretion in response to chlamydial 60 kDa heat shock protein amongst women with pelvic inflammatory disease and a history of repeated Chlamydia trachomatis infections. 1194 26

Cyclophosphamide is an alkylating agent used to treat malignancies and immune-mediated inflammatory non-malignant processes such as lupus nephritis and immune-mediated neuropathies. It has been studied as a treatment for multiple sclerosis (MS) for the past 30 years and is used by physicians in selected cases of progressive or worsening MS. Review of published reports suggests that it is efficacious in cases of worsening MS that have an inflammatory component as evidenced by relapses and/or gadolinium (Gd)-enhancing lesions on magnetic resonance imaging (MRI) or in patients in earlier stages of disease where inflammation predominates over degenerative processes in the central nervous system (CNS). There is no evidence of efficacy in primary progressive MS or later stages of secondary progressive MS. Although a general immunosuppressant that affects both T- and B-cell function, cyclophosphamide has selective immune effects in MS by suppressing IL-12 and Th1-type responses and enhancing Th2/Th3 responses (IL-4, IL-10, TGF-beta; eosinophils in peripheral blood). Side effects include nausea, alopecia, infertility, bladder toxicity and risk of malignancy. The most commonly used regimens involve every 4- to 8-week outpatient i.v. pulse therapy given with or without corticosteroids and are usually well-tolerated by patients. Cyclophosphamide is currently used in patients whose disease is not controlled by beta-interferon or glatiramer acetate and those with rapidly worsening MS.
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PMID:Treatment of multiple sclerosis with cyclophosphamide: critical review of clinical and immunologic effects. 1199 Aug 72

Chlamydia trachomatis-associated tubal factor infertility (TFI) involves enhanced humoral and cell-mediated immune response to the chlamydial 60 kDa heat shock protein (CHSP60). We evaluated the role of CHSP60-induced immune response in TFI by studying lymphocyte proliferation and cytokine (interferon (IFN)-gamma, interleukin (IL)-12 and IL-10) secretion in response to C. trachomatis elementary body (EB) and CHSP60 antigens in 57 women with TFI and in 76 women with other causes of infertility. Positive proliferative response of PBMC to CHSP60 was more common in the TFI group (20/57; 36%) than in the other groups (17/76; 22%) although the frequency or the median responses did not differ significantly (1.6, range 0.2-22.1 versus 1.4; 0.2-24.4). C. trachomatis EB induced significantly higher IFN-gamma and lower IL-10 secretion in the TFI group compared to the other groups. The EB and CHSP60 induced IL-12 secretion was similar in all study groups and correlated with IFN-gamma secretion in the other but not in the TFI group. The lack of correlation between EB-induced IL-12 and IFN-gamma production and simultaneously found prominent IL-10 secretion in response to CHSP60 in the TFI group suggests that the CHSP60 may have a specific role in regulating the immune reactions during chlamydial infection and may consequently contribute to the immunopathogenesis of TFI.
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PMID:Chlamydia trachomatis heat shock protein-60 induced interferon-gamma and interleukin-10 production in infertile women. 1256 92

A growing body of evidence suggests that endometriosis modulates the microenvironment of peritoneal cavity. Therefore, in this study, we compared the protein profile of peritoneal fluids from normal fertile women with those from patients with infertility, and patients with mild to severe endometriosis. Two-dimensional gel electrophoresis of peritoneal fluids from normal subjects exhibited a distinct and reproducible pattern of proteins in the size ranges of approximately 35 to 80 kD and pI close to 4.5 to 6.6. Infertility without evidence of endometriosis was not associated with changes in the relative abundance of proteins present in the peritoneal fluid. However, mild endometriosis was associated with a mild reduction in the amount of several peritoneal protein spots with the approximate molecular weights of 35-40 kD and pI close to 5.7-6.0. These changes became markedly apparent in the peritoneal fluid of patients who suffered from the severe form of this disease. Severe endometriosis was also associated with appearance of protein spots in the gels that were not detectable in the peritoneal fluids of normal subjects. Consistent with these data, enzyme-linked immunosorbent assay showed that moderate to severe endometriosis was associated with markedly elevated levels of IL-10 in the peritoneal fluid. Reverse transcription followed by polymerase chain reaction amplification using primers specific to IL-10 confirmed presence of IL-10 mRNA in cells derived from peritoneal fluids. These findings show that endometriosis is associated with disturbed secretion of proteins into the peritoneal cavity and with an elevated level of IL-10 in the peritoneal fluid. The studies also show cells resident in peritoneum as a major source of IL-10.
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PMID:Endometriosis is associated with alterations in the relative abundance of proteins and IL-10 in the peritoneal fluid. 1270 72

Evidence indicates that the testis possesses a reduced capacity to mount inflammatory and rejection responses, which undoubtedly contributes to the ongoing survival of the highly immunogenic germ cells. The contribution of local cytokine expression to this condition was investigated in adult male rats treated with lipopolysaccharide to induce inflammation. Cytokine mRNA and protein expression were determined in tissue extracts and fluids by Northern blot analysis, quantitative PCR, or RNAse protection assay and specific ELISAs. Testicular expression of the proinflammatory cytokines, interleukin (IL)-1beta and tumor necrosis factor-alpha was considerably attenuated compared with the liver (control tissue); in contrast, the testicular IL-6 response was enhanced. Expression of IL-10, a type 2 immunoregulatory cytokine, was similar in both testis and liver, whereas the immunoregulatory/anti-inflammatory cytokines transforming growth factor-beta(1) and activin A were constitutively elevated in both normal and inflamed testes. The IL-1beta and transforming growth factor-beta(1) proteins were present principally in their latent (inactive) forms, indicating that enzymic processing is an important control mechanism for these two cytokines within the testis. These data indicate that inflammatory and regulatory cytokine activity is regulated at both transcriptional and posttranslational levels in a testis-specific manner. It is concluded that a novel pattern of suppression of proinflammatory cytokine responses and normal or elevated expression of immunoregulatory cytokines may be responsible for reduced inflammatory responses and enhanced graft survival in the testis. These data have important implications for the understanding and treatment of male autoimmune infertility, testicular inflammation. and carcinogenesis.
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PMID:Cytokine profiles in the testes of rats treated with lipopolysaccharide reveal localized suppression of inflammatory responses. 1566 66

Chlamydia trachomatis, an intracellular obligate bacterium, remains responsible for a large spectrum of disorders that can progress to chronic diseases, resulting in severe sequelae, such as tubal infertility and blindness. These sequelae may be due to deleterious immune responses induced by repeated or persistent infections. By initiating and regulating inflammation as well as immune responses, pro-inflammatory cytokines secreted by local infected epithelial and immune cells, such as monocytes, may play an essential role in immunity and in the immunopathogenesis of chlamydial diseases. In this study, we mimicked the in vivo interaction between epithelial cells and monocytes by co-culturing epithelial-like HeLa cells with monocyte-like THP-1 cells. Pro-inflammatory cytokines [interleukin-beta (IL-1beta), IL-6, IL-8, IL-10, IL-12p70 and tumour necrosis factor-alpha (TNF-alpha)] were measured by multiplexed cytometric bead array assay over a period of 18 days. We observed that pro-inflammatory cytokine secretion was augmented after C. trachomatis infection in HeLa and THP-1 cells. However, this heightened secretion was subsequently reduced. When infected HeLa cells were co-cultured with THP-1 cells, IL-6 and IL-8 secretion was sustained, IL-1beta expression followed a bell-shaped curve and IL-10, IL-12p70 and TNF-alpha synthesis was down regulated. IL-6 and IL-8 may be involved in the immunopathogenesis of chronic chlamydial infections. We also observed that throughout C. trachomatis persistence induced by doxycycline (Dox) treatment, IL-1beta, IL-6, IL-8 and TNF-alpha expression was reduced, whereas the synthesis of IL-10 and IL-12p70 remained unchanged but not sustained. Thus, during chlamydial persistence infection evoked by treatment with Dox, none of the tested cytokines showed sustained expression.
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PMID:Sustained interleukin-6 and interleukin-8 expression following infection with Chlamydia trachomatis serovar L2 in a HeLa/THP-1 cell co-culture model. 1649 73

A receptive endometrial environment requires adequate immunological tolerance to protect the implanting embryo from maternal immune rejection. Studies in mice implicate CD4+CD25+ T-regulatory (Treg) cells as essential mediators of immune tolerance in pregnancy. The aim of this study was to evaluate the link between Treg cells and fertility in women. Expression of Foxp3, a master regulator of Treg cell differentiation, was quantified in endometrial tissue from women experiencing primary unexplained infertility and normal fertile women. Endometrial biopsies were collected during the mid-secretory phase of the menstrual cycle from women meeting rigorously defined criteria for unexplained infertility after experiencing repeated failed cycles of IVF treatment (infertile, n = 10), or women classified as proven fertile (control, n = 12). Expression of Foxp3 mRNA was reduced approximately two-fold in the tissue of infertile women. In contrast, mRNAs encoding T cell transcription factors T-bet and GATA3, associated with differentiation of Th1 and Th2 CD4+ T cells respectively, were unchanged. Treg cell differentiation is controlled by TGFbeta, but the relative abundance in endometrial tissue of TGFbeta1, TGFbeta2, TGFbeta3 mRNAs was not changed in infertile women. Cytokines influencing Th1 and Th2 cell differentiation, including IFNgamma, IL-2, IL-4, IL-5, IL-10 and IL-12p40, as well as dendritic cell-regulating cytokines IL-1alpha, IL-1beta, IL-6, LIF, GM-CSF and TNFalpha were also expressed similarly regardless of fertility status. The finding of reduced endometrial Foxp3 implicates impaired differentiation of uterine T cells into the Treg phenotype as a key determinant of fertility in women. The factors underpinning this aberration in the immune response remain to be identified.
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PMID:Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. 1657 99

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