Dendritic cells (DCs) act as APCs in the airway and play a critical role in allergy. Cysteinyl leukotrienes (cysLTs) synthesized from arachidonic acid are primary mediators of immediate asthmatic reaction. The aim of this study was to investigate the effects of cysLTs on Dermatophagoides farinae (Der f)-pulsed mouse myeloid DCs in inducing allergic airway inflammation in vitro and in vivo. Control DC (medium-pulsed), Der f-pulsed DC, cysLT-pulsed DC, Der f- and cysLT-pulsed DC, and Der f-pulsed and cysLT receptor antagonist (LTRA)-treated DC were prepared from murine bone marrow, and the production of cytokines ws compared. Subsequently, these DCs were intranasally instilled into another group of naive mice, followed by intranasal Der f challenge to induce allergic airway inflammation in vivo. Der f-pulsed DC produced significantly higher amounts of IL-10 and IL-12 compared with control DC. Der f- and cysLT-pulsed DC further increased IL-10 production compared with Der f-pulsed DC. In contrast, treatment of Der f-pulsed DC with LTRA increased IL-12 and decreased IL-10. Intranasal instillation of Der f-pulsed DC resulted in airway eosinophilia associated with a significant rise in IL-5 levels in the airway compared with control DC. Pulmonary eosinophilia and excess IL-5 were further enhanced in Der f- and cysLT-pulsed DC-harboring mice. In contrast, Der f-pulsed and LTRA-treated DC significantly inhibited airway eosinophilia, reduced IL-5, and increased IFN-γ in the airway. Our results suggest that cysLTs play an important role in the development of allergic airway inflammation by regulating the immunomodulatory functions of DCs.

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Background: Steroid-induced adverse effects including suppression of humoral immunity should be considered in steroid-dependent severe asthma. Only a few studies have determined the exact steroid dose that could potentially suppress humoral immunity in asthmatics. Methods: Randomly selected 100 adult asthmatics treated with inhaled beclomethasone dipropionate (BDP) were classified into three groups based on the dose of steroid to determine the serum IgG, IgA and IgM levels by radioimmunoassay. Relationships between serum immunoglobulin levels and the daily dose and duration of oral prednisolone (PSL) therapy were examined. Results: None of the patients on inhaled corticosteroid alone had hypogammaglobulinemia. Patients on oral PSL at a dose >12.5 mg/day for at least 1 year had low serum IgG. There was no significant correlation between the duration of oral PSL therapy and serum IgG. Conclusions: Oral PSL can potentially suppress humoral immunity in severe asthma. In asthmatics, hypogammaglobulinemia could develop in those on a daily dose of PSL >12.5 mg, but is independent of the duration of such treatment. No suppression of humoral immunity was noted on inhaled corticosteroid therapy alone, either at low or high dose.

Our results suggest that inhaled corticosteroids can potentially decrease salivary total IgA but that host factors are also important in the development of oral candidiasis.

Backgrounds: Approximately half of the Japanese asthmatics experience exacerbation of asthma after alcohol consumption. We previously reported that this phenomenon is probably caused by histamine release from mast cells by acetaldehyde stimulation. However, no reports have described the effects of acetaldehyde on human airway mast cells. The purpose of the present study was to demonstrate acetaldehyde-induced histamine release from human airway mast cells with subsequent airway smooth muscle contraction and to investigate the ensuing mechanisms. Methods: Human tissue samples were prepared from the lungs resected from patients with lung cancer. The effect of acetaldehyde on airway muscle tone and the concentration of chemical mediators released in the organ bath were measured before and after acetaldehyde stimulation. Mast cells were prepared from lung parenchyma by the immunomagnetic method and then stimulated with acetaldehyde to determine the chemical mediators released. Results: Acetaldehyde (>3 × 10^–4M) increased airway muscle tone, which was associated with a significant increase in the release of histamine, but not thromboxane B₂ or cysteinyl-leukotrienes. A histamine (H₁ receptor) antagonist completely inhibited acetaldehyde-induced bronchial smooth muscle contraction. Acetaldehyde also induced a significant histamine release from human lung mast cells and degranulation of mast cells. Conclusions: The present results strongly suggest that acetaldehyde stimulates human airway mast cells to release histamine, which may be involved in bronchial smooth muscle contraction following alcohol consumption.