Differential immunogenic and neurogenic inflammatory responses in an allergic mouse model exposed to low levels of formaldehyde.
It is suspected that exposure to low levels of formaldehyde induces or aggravates airway inflammation mediated by immunological and neurological reactions. To clarify the effect of this exposure on allergic inflammatory responses, we exposed female C3H/He mice to 0, 80, 400, or 2000ppb formaldehyde for 12 weeks. When mice were immunized with ovalbumin (OVA) and then exposed to formaldehyde, the numbers of total bronchoalveolar lavage cells, macrophages, and eosinophils in the mice exposed to 2000ppb formaldehyde were significantly increased compared to 0ppb controls. However, the production of interleukin-1beta from bronchoalveolar lavage fluid of these mice decreased significantly. Immunization with OVA significantly increased the production of nerve growth factor, but exposure to 80 and 400ppb formaldehyde significantly reduced the nerve growth factor levels in bronchoalveolar lavage fluid of the immunized mice. In in vitro study, markedly increased lipopolysaccharide-stimulated interferon-gamma production in culture supernatants of spleen cells from 2000ppb formaldehyde-exposed, nonimmunized mice, and significantly increased OVA-stimulated monocyte chemoattractant protein-1 production in culture supernatants of spleen cells from 400 and 2000ppb formaldehyde-exposed, immunized mice were observed. Exposure to 400ppb formaldehyde induced significant decreases in anti-OVA IgG1 and IgG3 antibody productions in plasma, whereas anti-OVA IgE antibody production was not affected. In addition, the levels of nerve growth factor in plasma of 80 and 400ppb formaldehyde-exposed, immunized mice significantly decreased compared to 0ppb control, immunized mice. These results provide the first experimental evidence that low levels of long-term formaldehyde inhalation can induce differential immunogenic and neurogenic responses in allergic mice.
Fujimaki
Hidekazu
H
National Institute for Environmental Studies, Environmental Health Sciences Division, 16-2, Onogawa, Tsukuba, Ibaraki 305-8506, Japan. fujimaki@nies.go.jp
Kurokawa
Yoshika
Y
Kunugita
Naoki
N
Kikuchi
Makoto
M
Sato
Fusae
F
Arashidani
Keiichi
K
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde / Q000008:administration & dosage / Q000633:toxicity*; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D020932:Nerve Growth Factor / Q000097:blood*; D009929:Organ Size / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D018925:Chemokines; D017077:Culture Media, Conditioned; D007074:Immunoglobulin G; D005557:Formaldehyde; D010047:Ovalbumin; D020932:Nerve Growth Factor