Juha Jussila ^A1, Hannu Komulainen ^A2, Veli-Matti Kosma ^A3, Aino Nevalainen ^A4, Jukka Pelkonen ^A5, Maija-Riitta Hirvonen ^A6

^A1 Laboratory of Toxicology, National Public Health Institute, Kuopio, Finland
^A2 Laboratory of Toxicology, National Public Health Institute, Kuopio, Finland
^A3 Department of Pathology and Forensic Medicine, University of Kuopio, and Kuopio University Hospital, Kuopio, Finland
^A4 Laboratory of Environmental Microbiology, National Public Health Institute, Kuopio, Finland
^A5 Department of Clinical Microbiology, University of Kuopio, and Department of Clinical Microbiology, Kuopio University Hospital, Kuopio, Finland
^A6 Laboratory of Toxicology and Laboratory of Environmental Microbiology, National Public Health Institute, Kuopio, Finland
 

Abstract:

Microbial growth in moisture-damaged buildings has been associated with respiratory health effects, and the spores of the mycotoxin producing fungus Aspergillus versicolor are frequently present in the indoor air. To characterize the potential of these spores to cause harmful respiratory effects, mice were exposed via intratracheal instillation to a single dose of the spores of A. versicolor (1 2 10⁵, 1 2 10⁶, 5 2 10⁶, 1 2 10⁷, or 1 2 10⁸ spores), isolated from the indoor air of a moisture-damaged building. Inflammation and toxicity in lungs were evaluated 24 h later by assessment of biochemical markers and histopathology. The time course of the effects was investigated with the dose of 5 2 10⁶ spores for up to 28 days. The exposure to the spores increased transiently proinflammatory cytokine levels (tumor necrosis factor [TNF] f and interleukin [IL]-6) in bronchoalveolar lavage fluid (BALF). The cytokine responses were dose and time dependent. The highest cytokine concentrations were measured at 6 h after the dose, and they returned to the control level by 3 days. Moreover, the spores of A. versicolor recruited inflammatory cells into airways: Neutrophils peaked transiently at 24 h, macrophages at 3 days, and lymphocytes at 7 days after the dosing. The inflammatory cell response did not completely disappear during the subsequent 28 days, though no histopathological changes were seen at that time point. The spores did not induce expression of inducible nitric oxide synthase in lavaged cells. Only the highest spore dose (1 2 10⁸) markedly increased serum IL-6, increased vascular leakage, and caused cytotoxicity (i.e., increased levels of albumin, total protein, lactate dehydrogenase [LDH], and hemoglobin in BALF) in the airways. In summary, the spores of A. versicolor caused acute inflammation in mouse lungs. This indicates that they have potential to provoke adverse health effects in the occupants of moisture-damaged buildings.