title: The mycotoxins citrinin and gliotoxin differentially affect production of the pro-inflammatory cytokines tumour necrosis factor-alpha and interleukin-6, and the anti-inflammatory cytokine interleukin-10.
abstract: BACKGROUND
  Microbial growth is considered one of the major causes of indoor air problems. Moulds have been associated with asthma, allergy and a wide range of diffuse indoor air-related symptoms. However, mechanisms of the adverse health effects are not well understood.
  
  
  OBJECTIVE
  We hypothesized that the mycotoxins citrinin and gliotoxin could cause an imbalance between the secretion of the pro-inflammatory cytokines TNF-alpha and IL-6 and the anti-inflammatory cytokine IL-10.
  
  
  METHODS
  We investigated the influence of citrinin and gliotoxin on the human monocytic cell line Mono-Mac-6 (MM6) with and without lipopolysaccharide -stimulation. The levels of IL-10, IL-6 and TNF-alpha were analysed in cell culture supernatants by ELISA. Cell viability and cell apoptosis were measured by flow cytometry.
  
  
  RESULTS
  The strongest inhibition of cytokine secretion was found for IL-10. IL-6 levels were found to decrease in a dose-dependent manner along with reduced cell viability. TNF-alpha levels increased with low gliotoxin exposure (less than 100 ng/mL), but decreased significantly at 375 ng/mL and higher along with increased cell apoptosis and reduced cell viability. TNF-alpha levels were not reduced by citrinin exposure.
  
  
  CONCLUSIONS
  We observed a cytokine imbalance with a more pronounced reduction of IL-10 concentrations compared with those of TNF-alpha and IL-6. We suggest that low exposure doses of citrinin and gliotoxin (corresponding to less than 100 ng/mL gliotoxin and less than 10 mug/mL citrinin) may inhibit IL-10 and lead to increased risk of an inflammatory response with relative overproduction of TNF-alpha and IL-6. The findings and their clinical implications must be verified by human studies. However, we speculate that the observed biological effects may be of importance as they may partly explain the occurrence of diffuse general indoor air-related symptoms as well as the worsening of asthmatic inflammatory reactions experienced in mouldy environments.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. Lene.Johannessen@medisin.ntnu.no
authors.forename: L N
authors.initials: LN
authors.lastname: Johannessen
authors.forename: A M
authors.initials: AM
authors.lastname: Nilsen
authors.forename: M
authors.initials: M
authors.lastname: Løvik
mesh_terms: D016902:Air Pollution, Indoor; D000900:Anti-Bacterial Agents / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D002953:Citrinin / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005912:Gliotoxin / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002953:Citrinin; D005912:Gliotoxin