title: Kinetics of IFN-gamma and TNF-alpha gene expression and their relationship with disease progression after infection with Mycobacterium tuberculosis in guinea pigs.
abstract: OBJECTIVE
  Guinea pig is one of the most suitable animal models for Mycobacterium tuberculosis (M. tb) infection since it shows similarities to pulmonary infection in humans. Although guinea pig shows hematogenous spread of M. tb infection into the whole body, immunological studies have mainly focused on granulomatous tissues in lungs and spleens. In order to investigate the time-course of disease pathogenesis and immunological profiles in each infected organ, we performed the following approaches with guinea pigs experimentally infected with M. tb over a 22-week post-infection period.
  
  
  METHODS
  We examined body weight changes, M. tb growth curve, cytokine gene expression (IFN-γ and TNF-α), and histopathology in liver, spleen, lungs and lymph nodes of infected guinea pigs.
  
  
  RESULTS
  The body weights of infected guinea pigs did not increase as much as uninfected ones and the number of M. tb bacilli in their organs increased except bronchotracheal lymph node during the experimental period. The gene expression of IFN-γ and TNF-α was induced between 3 and 6 weeks of infection; however, kinetic profiles of cytokine gene expression showed heterogeneity among organs over the study period. Histophathologically granulomatous lesions were developed in all four organs of infected guinea pigs.
  
  
  CONCLUSIONS
  Although IFN-γ and TNF-α gene expression profiles showed heterogeneity, the granuloma formation was clearly observed in every organ regardless of whether the number of bacilli increased or decreased. However, this protective immunity was accompanied with severe tissue damage in all four organs, which may lead to the death of guinea pigs.
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
authors.forename: In Soon
authors.initials: IS
authors.lastname: Roh
authors.forename: Sungae
authors.initials: S
authors.lastname: Cho
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Eum
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
mesh_terms: D000818:Animals; D001835:Body Weight; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D009169:Mycobacterium tuberculosis; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D014376:Tuberculosis / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: IFN-γ; Mycobacterium tuberculosis; TNF-α; guinea pigs; pathogenesis
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