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The mycotoxins citrinin and gliotoxin differentially affect production of the pro‐inflammatory cytokines tumour necrosis factor‐α and interleukin‐6, and the anti‐inflammatory cytokine interleukin‐10
Author(s) -
Johannessen L. N.,
Nilsen A. M.,
Løvik M.
Publication year - 2005
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2005.02249.x
Subject(s) - gliotoxin , citrinin , cytokine , tumor necrosis factor alpha , viability assay , immunology , interleukin 10 , interleukin , lipopolysaccharide , biology , apoptosis , mycotoxin , aspergillus fumigatus , biochemistry , food science
Summary 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‐α 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‐α 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‐α 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‐α levels were not reduced by citrinin exposure. Conclusion We observed a cytokine imbalance with a more pronounced reduction of IL‐10 concentrations compared with those of TNF‐α 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 μg/mL citrinin) may inhibit IL‐10 and lead to increased risk of an inflammatory response with relative overproduction of TNF‐α 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.