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There is increasing concern about multiple high concentration exposure to toxins in disaster and emergency situations. However, conventional toxicology testing methods may not adequately address these situations. Thus, we assessed whether the toxic effects of exposure in the adulthood differ depending on the presence or absence of neonatal exposure to Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in male rats to investigate the effects of exposure history of chemicals. In the neonatal stage [postnatal days (PNDs) 1-7], animals were treated with either sesame oil (5 ml/kg/day) as a control or TDCIPP (250 mg/kg/day) dissolved in sesame oil. In adulthood (PND 101-107), animals were treated with either sesame oil (5 ml/kg/day) or TDCIPP (650 mg/kg/day). One day after the final administration, dissection was performed, and body and organ weight, hematology, blood biochemistry, and histopathology were examined. The results demonstrated that the toxic effects of TDCIPP exposure in adulthood on adrenal gland size, serum iron content, and unsaturated iron binding capacity were enhanced by TDCIPP exposure in the neonatal stage. From these findings, it was indicated that the toxic effects of TDCIPP exposure in the adult stage are affected by pediatric exposure. These results suggest that the toxic effects of high-dose and long-term unsteady exposure to chemicals in large-scale disasters may change based on the exposure history of chemicals., (© 2022 John Wiley & Sons, Ltd.)

Bisphenol A (BPA) is a raw material of polycarbonate and epoxy resin. It is used for various household electrical appliances, electronic equipment, office automation equipment, medical equipment, mobile phones, paints for automobiles, internal surface coating of cans, and adhesives for civil engineering and construction. BPA is a well-known endocrine-disrupting chemical, and it was reported that BPA has an adverse effect on the nervous and immune systems. However, BPA-induced memory impairment and changes in neuroimmune biomarkers in the allergic asthmatic subject are not known yet. We aim to investigate the dietary exposure effect of BPA on brain function and biomarkers using allergic an asthmatic mouse model. Five-week-old male C3H/HeJSlc mice were fed two doses of BPA [0.901, 9.01 μg/kg/day] contained chow diet from 5 to 11 weeks old and ovalbumin (OVA) was given by intratracheal instillation every 2 weeks. Memory function was determined by a novel object recognition test. Genes related to memory and immune markers in the hippocampus were investigated with the real-time polymerase chain reaction (RT-PCR) method. In this study, impaired novel object recognition occurred in BPA-exposed mice in the presence of an allergen. Moreover, upregulation of expression level of neuroimmune biomarkers such as N-methyl-D-aspartate receptor, tumor necrosis factor-α, ionized calcium-binding adapter molecule-1, cyclooxygenase-2, and heme oxygenase-1 in the hippocampus was observed in BPA-exposed allergic asthmatic mice. These findings show that BPA exposure can induce neuroinflammation and which triggers impairment of memory function in mice with allergic asthma. Our study indicated that dietary exposure to BPA may affect higher brain functions by modulating neuroimmune biomarkers in allergic asthmatic subjects., (© 2021 John Wiley & Sons, Ltd.)

We compared the toxicokinetics of methylmercury (MeHg) in KK-Ay type 2 diabetic mice and C57BL/6J mice to evaluate how metabolic changes associated with diabetes affect MeHg toxicokinetics. A single dose of MeHg (0.2, 1, or 5 mg mercury/kg) was administered orally to 12-week-old KK-Ay and C57BL/6J male mice. Total mercury concentrations in plasma, blood cells, whole blood, and tissues (brain, kidneys, liver, and pancreas) were measured after 4, 7, 11, and 14 days. The volume of distribution/bioavailability and the elimination rate constant per day were higher in KK-Ay mice, while the terminal elimination half-life was lower in almost all samples of KK-Ay mice. The area under the curve was lower in all blood and almost all tissue samples from KK-Ay mice. Total clearance/bioavailability was lower in all blood and tissue samples of KK-Ay mice at all MeHg doses. These results indicate that MeHg is more rapidly absorbed by, and eliminated from, the blood cells, brain, liver, kidney, and pancreas of KK-Ay mice under the experimental conditions. Different patterns of tissue-to-plasma and tissue-to-whole blood partition coefficients suggest that notable differences in MeHg transfer between plasma and blood cells affect its distribution in tissues of the two mouse strains. These findings are useful to understand the selective distribution of MeHg to target organs and the sensitivity to MeHg in pathological states., (© 2020 John Wiley & Sons, Ltd.)

The widespread use of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) as a flame retardant has led to its release to the environment. Thus, the toxicological effects of TDCIPP on humans and animals are of importance. For better understanding of its potential toxicities, TDCIPP (250, 500, or 650 mg/kg/day) or vehicle control was administrated orally to adult male Wistar-Imamichi rats for 7 days. After the final administration of compounds, organ weights, histopathology, blood biochemistry, and hematology were examined. Hepatic toxicity was observed at doses ≥ 500 mg/kg/day of TDCIPP, and renal toxicity was observed at 650 mg/kg/day. The anti-androgenic activity of TDCIPP was previously confirmed in vitro and in vivo, but weights of epididymis, an androgen-dependent organ, were not affected by TDCIPP treatment in adults. Serum alkaline phosphatase activity was significantly decreased in all TDCIPP-treated rats independent of dose. Hemoglobin concentration, hematocrit, red blood cell count, and reticulocyte count were decreased in all TDCIPP-treated rats, but mean corpuscular volume, total iron-binding capacity, and serum iron were normal, suggesting that renal anemia was caused by TDCIPP. Together with previous reports on effects of anti-androgenic substances on red blood cell indices, anemia caused by TDCIPP could be due to its anti-androgenic activity. These considerations will contribute to further assessment of the toxicity of the compound., (© 2020 John Wiley & Sons, Ltd.)

Tris(2-butoxyethyl) phosphate (TBEP) is a major organophosphorus flame retardant and has been widely increasing as a substitute for brominated flame retardants. TBEP may have adverse effects on human health; however, its impact on immune and allergic responses remains largely uncharacterized. In this study, the effects of low-dose TBEP comparable with the level of actual human exposure to that of human tolerable daily intake on allergic asthmatic mice were explored. Five-week-old C3H/HeJSlc male mice consumed a diet containing approximately 0.02, 0.2 or 2 μg/kg/day TBEP and were intratracheally administrated ovalbumin (OVA) (1 μg/mouse every 2 weeks from 5 to 11 weeks of age). Exposure to 2 μg/kg/day TBEP with OVA tended to enhance allergic pulmonary inflammation and significantly elevated mRNA levels of interleukin-5, eotaxin-1 and estrogen receptor alpha (ERα) compared with OVA alone. In mediastinal lymph nodes (MLNs), TBEP (0.2 or 2 μg/kg/day) with OVA significantly increased in total cell number and promoted conventional dendritic cell activation than OVA alone; MLN cell proliferation by OVA restimulation was also enhanced in these groups. In the bone marrow (BM), TBEP (0.02 or 0.2 μg/kg/day) with OVA resulted in a net decrease in total cell number and fraction of CCR2 + Gr-1 + cells; the fraction of Gr-1 + cells increased. In conclusion, oral exposure to low-dose TBEP levels equivalent to tolerable daily intake may exacerbate allergic pulmonary inflammation by promoting a skewed T-helper 2 cell response, upregulation of ERα and dysregulation of both MLN and BM microenvironments., (© 2020 John Wiley & Sons, Ltd.)

Methylmercury (MeHg) is known to cause neurobehavioral impairment in human and experimental animals. We previously reported that MeHg (5 mg Hg/kg) induced severe neurobehavioral dysfunction in 4-week-old KK-Ay mice, although it is difficult to evaluate quantitatively the neurobehavioral impairment in MeHg-treated KK-Ay mice because of their obesity. The aim of this study was to evaluate MeHg-induced neurobehavioral dysfunction in KK-Ay mice using the dynamic weight-bearing test, which analyzes the animal's weight distribution between the four limbs. Male 12-week-old KK-Ay mice were treated with MeHg (5 mg Hg/kg) three times per week for 5 weeks. Body weight loss began after approximately 2 weeks of MeHg treatment, and decreased significantly at 4 weeks. Seven of the nine MeHg-treated mice exhibited overt neurological symptoms such as ataxia and gait disturbance. The weight-bearing load was lower for the forelimb than for the hindlimb at baseline and until 1 week after MeHg treatment was initiated. In weeks 2-4, the dynamic weight-bearing loads on the forelimb and hindlimb were similar. The load on the forelimb exceeded the load on the hindlimb after 5 weeks of treatment. This finding indicates that the dynamic weight-bearing test is useful for semi-quantitative evaluation of neurobehavioral impairment in MeHg-treated rodents, and is less stressful for the animals. Infiltration of CD204-positive macrophages was observed in the sciatic nerve of MeHg-treated mice, suggesting that CD204 can serve as a useful marker of tissue injury in peripheral nerves and a possible target in regenerating peripheral nerves and controlling neuropathies., (© 2018 John Wiley & Sons, Ltd.)

The accumulation of macrophages has been observed around lesions of the brain in patients with Minamata disease. In this condition, mercury has been detected histochemically in macrophages throughout the brain. However, the role of macrophages in the neurotoxicity of methylmercury (MeHg) and the molecular mechanisms of their response to MeHg exposure remain to be elucidated. Here, we investigated how MeHg affects the expression of proinflammatory cytokines such as interleukin (IL)-6 and IL-8 in cultured human U937 macrophages. Compared with controls, IL-6 and IL-8 mRNA expression was maximally induced in U937 macrophages after treatment with 10 μM MeHg for 6 h. The protein secretion of IL-6 and IL-8 was significantly stimulated by MeHg in U937 macrophages. Results from luciferase reporter assay indicated functional activation of nuclear factor kappa B and the involvement of subunit RelA and p50 in MeHg-induced IL-6 and IL-8 activation, which was confirmed by siRNA knockdown experiments. MeHg exposure at 4 μM also significantly induced IL-8 expression in U-87 MG cells at mRNA and protein level, indicating that IL-8 induction might be a general mode of action of MeHg treatment among different cell types. These results indicate a possible involvement of an early inflammatory response, including IL-6 and IL-8 expression in the pathogenesis of MeHg. N-acetyl-l-cysteine suppressed MeHg-induced activation of IL-6 and IL-8 mRNA expression in U937 macrophages, indicating the effectiveness of N-acetyl-l-cysteine as a therapeutic drug in MeHg-induced inflammation. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Benzo[a]pyrene (BaP) reportedly has mutagenic and adjuvant activities. We aimed to determine the effects of low-dose BaP administration on allergic airway inflammation and mediastinal lymph node (MLN) cell activation/proliferation in mice. Male C3H/HeJ mice were intratracheally administered ovalbumin (OVA) every 2 weeks and/or BaP (0, 0.05, 1 and 20 pmol per animal per week) once per week for 6 weeks. The cellular profile of bronchoalveolar lavage (BAL) fluid, histological changes, inflammatory cytokines/chemokines in the lungs, OVA-specific immunoglobulin (Ig) in serum and MLN cell activation/proliferation were examined. BaP administration of 20 pmol with OVA enhanced neutrophil and macrophage accumulation in the lungs. Compared with OVA administration, BaP administration with OVA tended to enhance pulmonary eosinophilia and goblet cell hyperplasia. Furthermore, it increased the levels of interleukin (IL)-5, IL-13, IL-33, monocyte chemoattractant protein-1 and eotaxin in the lungs, and OVA-specific IgG1 in serum, although not dose-dependently. Compared with the vehicle group, IL-6 and tumor necrosis factor-alpha levels were higher in the OVA + 1 pmol BaP group and IL-12 production was higher in the OVA + 20 pmol BaP group. Ex vivo studies showed that co-exposure to OVA and BaP activated the MHC class II and CD86 expression in MLN cells. Exposure to BaP with OVA increased IL-4, IL-5 and interferon gamma levels in culture supernatants of OVA-re-stimulated MLN cells. In conclusion, low-dose BaP can, at least in part, enhance allergic airway inflammation by facilitating Th2 responses and activating MLN cells; a high BaP dose may contribute to activating both Th1 and Th2 responses. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

We examined the toxic effects of methylmercury (MeHg) in KK-Ay type 2 diabetic mice to clarify how metabolic changes associated with type 2 diabetes mellitus affect MeHg toxicity. MeHg (5 mg Hg kg (-1) day(-1) p.o.) was given to 4-week-old male KK-Ay and C57BL/6J (BL/6) mice three times per week for 6 weeks. Average body weights (BW) of vehicle-treated BL/6 and KK-Ay mice were 16.3 and 16.4 g respectively on the first day, and 24.8 and 42.3 g respectively on the last day of the experiment. MeHg-treated KK-Ay mice began to lose weight about 5 weeks after MeHg administration. Six of seven MeHg-treated KK-Ay mice showed hind-limb clasping in the final stage of the experiment. The mean blood mercury level of MeHg-treated KK-Ay mice reached a maximum of 9.8 µg ml(-1) , whereas that of the MeHg-treated BL/6 mice was 2.8 µg ml(-1) after 10 days of treatment. The average total mercury concentrations in the cerebrum and epididymal fat pad were 7.4 and 0.57 µg g(-1) , respectively, for BL/6 mice and 27 and 1.6 µg g(-1) , respectively, for KK-Ay mice. In MeHg-treated KK-Ay mice with neurological symptoms, CD204-positive macrophages were observed in the brain, kidney and spleen, indicating CD204 could be a marker for injured tissues. BW loss and significant pathological changes were not observed in other groups of mice. These results indicate that body fat gain in type 2 diabetes mellitus and low mercury accumulation in adipose tissue increased MeHg concentrations in organs and enhanced toxicity in KK-Ay mice at the same dose of MeHg per BW., (Copyright © 2013 John Wiley & Sons, Ltd.)

Phthalate esters in plastics act as adjuvants for immunoglobulin production, which aggravates allergic disease. However, the effects of alkylphenols (used as plasticizers and surfactants) on atopic dermatitis have not been studied in detail. Therefore, the goal of the present study was to investigate the effects of the alkylphenols 4-nonylphenol (NP), 4-tert-octylphenol (OP) and 4-tert-butylphenol (BP) in a murine model of atopic dermatitis. NC/Nga mice were intraperitoneally administered NP, OP or BP and were subcutaneously injected with mite allergen in one ear to induce atopic dermatitis-like skin lesions (ADSLs). The condition of the skin was observed, and the levels of immunoglobulin in serum and inflammatory cytokines in lesions were determined. NP exacerbated mite allergen-induced ADSLs according to dose. OP and BP also significantly exacerbated skin lesions but not as a function of dose. Alkylphenols tended to increase the levels of IgE and antigen-specific IgG1 in serum. Further, the treatment of the alkylphenols increased the expression in lesions of inflammatory cytokines, interleukin-4 and monocyte chemotactic protein-3. Thymic stromal lymphopoietin levels increased according to ADSL severity. In contrast, the levels of the T-helper 1 cytokines (interleukin-18 and interferon-gamma) decreased. NP, OP or BP may enhance T-helper 2-type immune responses in NC/Nga mice, which aggravates mite allergen-induced ADSLs. Therefore, the uptake of very low levels of alkylphenols may contribute to the increase in the incidence of atopic dermatitis., (Copyright © 2013 John Wiley & Sons, Ltd.)

Particulate matter can exacerbate respiratory diseases such as asthma. Diesel exhaust particles are the substantial portion of ambient particulate matter with a <2.5 µm diameter in urban areas. Epidemiological data indicate increased respiratory health effects of particulate matter in obese individuals; however, the association between obesity and diesel exhaust particle-induced airway inflammation remains unclear. We aimed to investigate the differences in susceptibility to airway inflammation induced by exposure to diesel exhaust particles between obese mice (db/db) and lean mice (db/+m). Female db/db and db/+m mice were intratracheally administered diesel exhaust particles or vehicle every 2 weeks for a total of seven times. The cellular profile of bronchoalveolar lavage fluid and histological changes in the lungs were assessed and the lungs and serum were analyzed for the generation of cytokines, chemokines and soluble intercellular adhesion molecule 1. Diesel exhaust particle exposure-induced eosinophilic infiltration in db/+m mice accompanied by T-helper 2 cytokine, chemokine and soluble intercellular adhesion molecule 1 expression in the lungs. In contrast, it induced mild neutrophilic airway inflammation accompanied by elevated cytokines and chemokines in db/db mice. The lungs of db/db mice exhibited decreased expression of eosinophil activators/chemoattractants such as interleukin-5, interleukin-13 and eotaxin compared with those of db/+m mice. In addition, serum eotaxin and monocyte chemotactic protein-1 levels were significantly higher in db/db mice than in db/+m mice. In conclusion, obesity can affect susceptibility to diesel exhaust particle-induced airway inflammation, which is possibly due to differences in local and systemic inflammatory responses between lean and obese individuals., (Copyright © 2013 John Wiley & Sons, Ltd.)

Brominated flame retardants (BFRs) are widely used in consumer products. Their toxicological effects as endocrine disruptors have been partly examined. However, their immunological effects have not been elucidated. To evaluate the effects of BFRs on immune responses, we investigated whether BFRs affect phenotypes and the function of immune cells in vitro. Here we examined the commercial pentabromodiphenyl ether mixture (DE-71), octabromodiphenyl ether mixture (DE-79), decabromodiphenyl ether mixture (DE-83R), hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA). Splenocytes and bone marrow (BM) cells were prepared from atopic prone NC/Nga mice. Splenocytes were exposed to each BFR for 24 h. BM cells were cultured with granulocyte macrophage-colony stimulating factor (GM-CSF) for 8 days and BM-derived dendritic cells (BMDCs) were exposed to each BFR for 24 h. In another experiment, BM cells were cultured with GM-CSF in the presence of each BFR for 6 days during BMDC differentiation. After exposure, cell surface molecule expression and cytokine production were investigated. Each BFR increased MHC class II and CD86 expression and interleukin (IL)-4 production in splenocytes. DE-71, HBCD and TBBPA increased T cell receptor (TCR) expression in splenocytes. In both experiments, all BFRs except TBBPA increased DEC205 expression in BMDCs. BMDCs that differentiated in the presence of HBCD showed enhanced MHC class II, CD80, CD86 and CD11c expression. The results demonstrate that some BFRs may stimulate immune cells. BFRs can induce or enhance immune/allergic responses by increasing antigen presentation-related molecule expression and IL-4 production., (Copyright © 2012 John Wiley & Sons, Ltd.)

Previously, we demonstrated that maternal exposure to phthalates enhances atopic dermatitis in male mouse offspring. However, whether phthalate exposure affects neuroimmune biomarkers in allergic mice has not yet been studied. Di-(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DINP) are environmental chemicals that are commonly used as plasticizers. This study was designed to investigate the expression levels of neuroimmune biomarkers in the hypothalamus of a murine model of allergic asthma after phthalate exposure throughout juvenility until adulthood. Six-week-old C3H/HeJ Jcl male mice were treated with DEHP or DINP (0, 0.02, 0.4 or 8 nmol per body per week) and ovalbumin (OVA; 1 µg per body per 2 weeks) for 7 weeks intratracheally. On the day after the completion of the phthalate and OVA treatment, the hypothalamus from each mouse was collected, and the mRNA expression levels of neuroimmune biomarkers were examined using a real-time RT-PCR analysis. The mRNA expression levels of the proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α, the chemokine CCL3, the transcription factor nuclear factor (NF)-κB, the oxidative stress marker heme-oxygenase (HO)1, a nerve growth factor, and the microglia marker Iba1 were remarkably up-regulated in the hypothalami of mice treated with 8 nmol of DEHP in the presence of the allergen. However, no significant changes were observed, except for reductions in the TNF-α and CCL2 mRNA levels, in mice exposed to DINP combined with the allergen. This study is the first report to show that high-dose DEHP exposure throughout juvenility until adulthood may induce neuroinflammation by modulating neuroimmune biomarkers in the hypothalami of allergic mice., (Copyright © 2012 John Wiley & Sons, Ltd.)

It was previously shown that pulmonary exposure of mice to diesel exhaust particles (DEP) enhances inflammatory conditions induced by allergens or bacterial endotoxin (lipopolysaccharide: LPS) via enhanced local expression of cytokines. However, resolution of the underlying mechanisms, in which DEP exaggerate inflammation, remains uncompleted. Investigation of the actions of DEP on mouse-derived mononuclear cells may provide a clue to the mechanisms, because mononuclear cells produce and release several types of cytokines. The present study elucidated the effects of DEP on mononuclear cell reactions stimulated with LPS in vitro. ICR mouse-derived mononuclear cells, isolated from splenocytes, one of the secondary lymphoid tissues, were co-cultured with LPS (1 microg ml(-1)) and DEP (1, 10 or 100 microg ml(-1)). The protein levels of interferon (IFN)-gamma, interleukin (IL)-2, IL-10, and IL-13 in the culture supernatants were measured 72 h after the co-culture. LPS significantly increased the protein levels of IFN-gamma, IL-2 and IL-10. In the presence of LPS, DEP decreased the protein levels in a concentration-dependent manner with an overall trend, whereas DEP (1, 10 microg ml(-1)) moderately elevated the IL-13 level. These results suggest that DEP suppress cytokine production from mononuclear cells stimulated with LPS and provide a possible hint for DEP facilitation on inflammatory conditions, especially related to Th2 response, in vivo., (Copyright 2006 John Wiley & Sons, Ltd.)

Although several studies have reported that diesel exhaust particles (DEP) affect cardiorespiratory health in animals and humans, the responsible components in DEP for the effects remain to be defined. Diesel exhaust particles contain quinones that can catalyse the generation of reactive oxygen species, resulting in the induction of oxidative stress. Oxidative stress can correlate with a variety of diseases and health effects. In the present study, we investigated the effects of phenanthraquinone--a relatively abundant quinone in DEP--on lung inflammation and the local expression of cytokine proteins in mice as a measure of oxidative damage. The animals were randomized into two experimental groups that received vehicle or phenanthraquinone by intratracheal instillation. The cellular profiles of bronchoalveolar lavage fluid (BALF) and local expression of cytokines were evaluated 24 and 48 h after the instillation. Phenanthraquinone challenge revealed an increase in the numbers of neutrophils and eosinophils in BALF as compared to vehicle challenge (P < 0.05 at 48 h post-instillation). Phenanthraquinone induced the lung expression of interleukin (IL)-5 and eotaxin 48 h and 24 h after the challenge, respectively. These results indicate that intratracheal exposure to phenanthraquinone induces recruitment of inflammatory cells, at least partly, through the local expression of IL-5 and eotaxin., (Copyright 2005 John Wiley & Sons, Ltd.)

We have reported previously that components of diesel exhaust particles (DEP) differently affect acute lung injury related to lipopolysaccharide (LPS) in mice. This study examined the effects of components of DEP on the lung expression of cyclooxygenase (COX)-1 and -2 in the presence or absence of LPS. ICR mice were divided into six experimental groups that received vehicle, LPS (2.5 mg kg(-1)), organic chemicals in DEP (DEP-OC) extracted with dichloromethane (4 mg kg(-1)), residual carbonaceous nuclei after the extraction (washed DEP: 4 mg kg(-1)), DEP-OC (4 mg kg(-1)) + LPS (2.5 mg kg(-1)) or washed DEP (4 mg kg(-1)) + LPS (2.5 mg kg(-1)) intratracheally. The expression of mRNA for both COXs in the lung was evaluated 4 h after the intratracheal administration. The magnitude of COX-1 mRNA expression was not altered in each group. The LPS treatment enhanced the COX-2 gene expression compared with vehicle treatment. Washed DEP combined with LPS further increased its expression compared with LPS alone. In contrast, combined treatment of DEP-OC with LPS decreased COX-2 gene expression compared with LPS alone. These results suggest that the residual carbonaceous nuclei of DEP predominantly enhance lung expression of COX-2 rather than the extracted organic chemicals from DEP in the presence of LPS, which is concomitant with the magnitude of acute lung injury in our previous study.

Response differences by different strains of mice towards house dust mites (Dermatophagoides farinae) or diesel exhaust particles (DEP) were investigated. Mouse strains BALB/c, ICR and C3H/He received 1 micro g of D. farinae or 1 microg of D. farinae + 50 microg of DEP intratracheally four times at 2-week intervals. Dermatophagoides farinae treatment caused the recruitment of eosinophils and lymphocytes. The order of magnitude of the eosinophilic airway inflammation was BALB/c < ICR < C3H/He mice. The protein levels of eotaxin and IL-5 in lung tissues correlated with the manifestations of eosinophilic airway inflammation by D. farinae administration. Diesel exhaust particles aggravated the manifestation of the eosinophilic inflammation through goblet cell proliferation in the airway and enhanced the local expression of eotaxin and IL-5 in all three strains of mice. The levels of eotaxin and IL-5 in lung tissues corresponded to the pathological changes caused by D. farinae + DEP. The increasing order of production levels of antigen-specific IgG1 by D. farinae or D. farinae + DEP was BALB/c < ICR < C3H/He mice. The significant adjuvant effect of DEP on IgG1 production was observed in the C3H/He mice (P < 0.05). These results suggest that the murine strain differences in the production of eosinophilic airway inflammation by D. farinae + DEP are related to differences in local expression of IL-5 and eotaxin. The enhancing effects of DEP may be mediated by a cytokine increase in the local expression. Antigen-specific IgG1 may be an important immunoglobulin in the pathogenesis of allergic asthma enhanced by DEP., (Copyright 2004 John Wiley & Sons, Ltd.)