During the course of establishing an animal model of chronic asthma, we tried to elucidate the time sequence of airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, and associated cytokines. Seven-week-old female BALB/c mice were studied as a chronic asthma model using ovalbumin (OVA). After sensitization, mice were exposed twice weekly to aerosolized OVA, and were divided into three groups depending on the duration of 4 weeks, 8 weeks, and 12 weeks. At each time point, airway responsiveness, inflammatory cells, cytokines in bronchoalveolar lavage fluids (BALF), serum OVA-specific IgE, IgG1, IgG2a, and histological examination were carried out. AHR to methacholine, increased levels of OVA-specific IgG1 and IgG2a, and goblet cell hyperplasia were continuously sustained at each time point of weeks. In contrast, we observed a time-dependent decrease in serum OVA-specific IgE, BALF eosinophils, BALF cytokines such as IL-13, transforming growth factor-beta1, and a time-dependent increase in BALF promatrix metalloproteinase-9 and peribronchial fibrosis. In this OVA-induced chronic asthma model, we observed airway remodelings as well as various cytokines and inflammatory cells being involved in different time-dependent manners. However, increased airway fibrosis did not directly correlate with a further increase in airway hyperresponsiveness.
Time Factors ; Pneumonia/chemically induced/*immunology ; Ovalbumin ; Mice, Inbred BALB C ; Mice ; Lung/drug effects/*immunology ; Female ; *Disease Models, Animal ; Cytokines/*immunology ; Chronic Disease ; Asthma/chemically induced/*immunology ; Animals

Allergic airway diseases are related to exposure to atmospheric pollutants, which have been suggested to be one factor in the increasing prevalence of asthma. Little is known about the effect of ozone and diesel exhaust particulates (DEP) on the development or aggravation of asthma. We have used a mouse asthma model to determine the effect of ozone and DEP on airway hyperresponsiveness and inflammation. Methacholine enhanced pause (P(enh)) was measured. Levels of IL-4 and IFN-gamma were quantified in bronchoalveolar lavage fluids by enzyme immunoassays. The OVA-sensitized-challenged and ozone and DEP exposure group had higher P(enh) than the OVA-sensitized-challenged group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone exposure group. Levels of IFN-gamma were decreased in the OVA-sensitized-challenged and DEP exposure group and the OVA-sensitized-challenged and ozone and DEP exposure group compared to the OVA-sensitized-challenged and ozone exposure group. Levels of IL-4 were increased in the OVA-sensitized-challenged and ozone exposure group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone and DEP exposure group compared to OVA-sensitized-challenged group. Co-exposure of ozone and DEP has additive effect on airway hyperresponsiveness by modulation of IL-4 and IFN-gamma suggesting that DEP amplify Th2 immune response.
Air Pollutants, Environmental/toxicity ; Animals ; Asthma/*chemically induced/*immunology ; Disease Models, Animal ; Drug Combinations ; Drug Synergism ; Female ; Hypersensitivity/complications/*etiology/*immunology ; Interferon Type II/immunology ; Interleukin-4/immunology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Ozone/*toxicity ; Pneumonia/*chemically induced/complications/*immunology ; Research Support, Non-U.S. Gov't ; Respiratory Hypersensitivity/chemically induced/complications/immunology ; Vehicle Emissions/*toxicity

Drug-induced neutropenia (DIN), particularly that in which antibiotic-dependent antineutrophil antibodies have been detected, is a rare disorder. We report the case of a child with pneumococcal pneumonia, who experienced severe neutropenia during various antibiotic treatments. We detected 4 kinds (cefotaxim, augmentin, vancomycin, and tobramycin) of antibiotic-dependent antineutrophil antibodies by using the mixed passive hemagglutination assay (MPHA) technique with this child.
Anti-Bacterial Agents/*therapeutic use ; Antibodies, Antineutrophil Cytoplasmic/*blood/immunology ; Autoantibodies/blood/immunology ; Drug Therapy, Combination ; Humans ; Infant ; Male ; Neutropenia/chemically induced/*diagnosis ; Pneumonia, Pneumococcal/complications/*drug therapy ; Tomography, X-Ray Computed

OBJECTIVETo examine the presence of gender differences in pulmonary inflammation evoked by acute systemic cadmium administration in rats.

METHODSPresence of basic indicators of lung inflammation (inflammatory cytokine lung content, leukocyte infiltration and activity of cells recovered from lungs by enzyme digestion) was analyzed and compared in animals of the two sexes.

RESULTSIntraperitoneal administration of cadmium (1.0 mg/kg) resulted in higher cadmium content in lungs of female rats. Higher tumor necrosis factor (TNF) content was noted in lung homogenates of male rats, while interleukin-6 (IL-6) content was slightly, but significantly greater in lungs of female rats. Increased leukocyte infiltration was observed in lungs of male rats, mainly due to neutrophils. Increased responsiveness to phorbol myristate acetate (PMA) stimulation was noted in cells recovered from lungs of male rats. Rise in intracellular content of myeloperoxidase (MPO) was noted in lung cells from cadmium-treated rats of both sexes, but higher in cells from male rats.

CONCLUSIONSPresented data documented a more intense pulmonary inflammatory response to systemic cadmium administration in males, with higher IL-6 levels in lungs of female individuals. These sex differences in proinflamatory activity of cadmium in lungs should be taken into consideration in studying the remote toxicity of this heavy metal.

Animals ; Cadmium Chloride ; pharmacokinetics ; toxicity ; Cytokines ; immunology ; Environmental Pollutants ; pharmacokinetics ; toxicity ; Enzyme-Linked Immunosorbent Assay ; Female ; Leukocyte Count ; Leukocytes ; cytology ; immunology ; Lung ; drug effects ; immunology ; metabolism ; Male ; Neutrophil Infiltration ; immunology ; Peroxidase ; metabolism ; Pneumonia ; chemically induced ; immunology ; metabolism ; Rats ; Rats, Inbred Strains ; Sex Characteristics