title: In infertile women, cells from Chlamydia trachomatis infected sites release higher levels of interferon-gamma, interleukin-10 and tumor necrosis factor-alpha upon heat-shock-protein stimulation than fertile women.
abstract: BACKGROUND
  The magnitude of reproductive morbidity associated with sexually transmitted Chlamydia trachomatis infection is enormous. Association of antibodies to chlamydial heat shock proteins (cHSP) 60 and 10 with various disease sequelae such as infertility or ectopic pregnancy has been reported. Cell-mediated immunity is essential in resolution and in protection to Chlamydia as well as is involved in the immunopathogenesis of chlamydial diseases. To date only peripheral cell mediated immune responses have been evaluated for cHSP60. These studies suggest cHSPs as important factors involved in immunopathological condition associated with infection. Hence study of specific cytokine responses of mononuclear cells from the infectious site to cHSP60 and cHSP10 may elucidate their actual role in the cause of immunopathogenesis and the disease outcome.
  
  
  METHODS
  Female patients (n = 368) attending the gynecology out patient department of Safdarjung hospital, New Delhi were enrolled for the study and were clinically characterized into two groups; chlamydia positive fertile women (n = 63) and chlamydia positive infertile women (n = 70). Uninfected healthy women with no infertility problem were enrolled as controls (n = 39). cHSP60 and cHSP10 specific cytokine responses (Interferon (IFN)-gamma, Interleukin (IL)-10, Tumor Necrosis Factor (TNF)-alpha, IL-13 and IL-4) were assessed by ELISA in stimulated cervical mononuclear cell supernatants.
  
  
  RESULTS
  cHSP60 and cHSP10 stimulation results in significant increase in IFN-gamma (P = 0.006 and P = 0.04 respectively) and IL-10 levels (P = 0.04) in infertile group as compared to fertile group. A significant cHSP60 specific increase in TNF-alpha levels (P = 0.0008) was observed in infertile group as compared to fertile group. cHSP60 and cHSP10 specific IFN-gamma and IL-10 levels were significantly correlated (P < 0.0001, r = 0.54 and P = 0.004, r = 0.33 respectively) in infertile group.
  
  
  CONCLUSIONS
  Our results suggest that exposure to chlamydial heat shock proteins (cHSP60 and cHSP10) could significantly affect mucosal immune function by increasing the release of IFN-gamma, IL-10 and TNF-alpha by cervical mononuclear cells.
authors.affiliation: Institute of Pathology - ICMR, Safdarjung Hospital Campus, Post Box no, 4909, New Delhi-110 029, India. pragyasr@rediffmail.com
authors.forename: Pragya
authors.initials: P
authors.lastname: Srivastava
authors.forename: Rajneesh
authors.initials: R
authors.lastname: Jha
authors.forename: Sylvette
authors.initials: S
authors.lastname: Bas
authors.forename: Sudha
authors.initials: S
authors.lastname: Salhan
authors.forename: Aruna
authors.initials: A
authors.lastname: Mittal
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002584:Cervix Uteri / Q000473:pathology; D018835:Chaperonin 10 / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D018834:Chaperonin 60 / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D002690:Chlamydia Infections / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D002692:Chlamydia trachomatis / Q000276:immunology / Q000502:physiology*; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D002575:Uterine Cervicitis / Q000209:etiology / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D018835:Chaperonin 10; D018834:Chaperonin 60; D006360:Heat-Shock Proteins; C508609:IL10 protein, human; C508598:IL4 protein, human; D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma