Clinical & Experimental Allergy Reviews最新文献

The cysteinyl leukotrienes (CysLTs) are lipid mediators that have been implicated in the pathogenesis of allergic diseases. Pharmacological studies using CysLTs indicate that there exist two classes of receptors named CysLT₁ and CysLT₂. The former is sensitive to CysLT₁ receptor antagonists currently used for the treatment of asthma and allergic rhinitis. Our previous immunohistochemical and autoradiographic studies showed that anti-CysLT₁ receptor antibody adhered to eosinophils, mast cells, macrophages, neutrophils, and vascular endothelial cells in human nasal mucosa, and that a novel radioactive CysLT₁ receptor antagonist, [³H]-pranlukast, bound specifically to CysLT₁ receptors in human inferior turbinate and its binding sites were localized to vascular endothelium and interstitial cells. These data suggest that in allergic rhinitis, the major targets of CysLT₁ receptor antagonists are the vascular bed and infiltrating leucocytes such as mast cells, eosinophils, and macrophages. Clinical trials have demonstrated that CysLT₁ receptor antagonists are as effective as antihistamines, but are less effective than intranasal steroids for the treatment of allergic rhinitis. The use of CysLT₁ receptor antagonists in combination with antihistamines has generally resulted in greater efficacy than when these agents were used alone.

Cytokine imbalance and cellular migration to inflammatory sites are critical components of allergic diseases. Redirecting cytokine imbalance and inhibiting cell migration therefore represent important therapeutic strategies for the treatment of these disorders. We studied the in vitro effect of the non-sedating H₁-receptor antagonists ebastine, carebastine, epinastine, cetirizine, and ketotifen on cytokine secretion by human T cells under various co-stimulatory conditions and the migratory activity of activated T cells as well as production of pro-inflammatory cytokines by macrophages. Ebastine and carebastine inhibited T cell proliferation and production of IL-4, IL-5, IL-6, and TNF-α by T cells under co-stimulation with CD28 plus CD3, CD26 plus CD3, and CD3 plus phorbol myristate acetate, whereas these drugs had no effect on the production of IL-2 and IFN-γ. Ebastine and carebastine also inhibited T cell migration and production of TNF-α and IL-6 by macrophages. Epinastine inhibited T cell proliferation and production of IL-2, IFN-γ, IL-4, and IL-5, whereas it elicited no effect on the production of IL-6 and TNF-α by T cells and macrophages as well as T cell migration. Cetirizine and ketotifen had no effects on cytokine production and T cell migration. Our results suggest that certain H₁-receptor antagonists, most notably ebastine and carebastine, can influence T cell migration and cytokine production in addition to antagonizing the H₁ receptor. These drugs therefore might be useful against T cell-mediated allergic inflammatory disorders such as asthma, atopic dermatitis, and psoriasis.

For basic and clinical studies of Japanese cedar (JC) pollinosis and its treatment, experimental facilities for exposure to pollen under stable environmental conditions are becoming increasingly desirable. We developed an artificial exposure chamber (OHIO Chamber) that allows the dispersal of fixed concentrations of JC pollen in stable environments with a unique pollen supply system, air flow system for fixing the concentration of JC pollen, system for monitoring the number of pollen grains, and automated pure water washing and drying system. In the chamber, temperature and relative humidity (RH) could be successfully maintained at 22±1.1 °C and 45±5%, respectively. The spatial distribution of pollen concentrations in the chamber was within 10% of target, including when subjects were present. Only a few or no pollen grains were detected in the chamber after automatic washing and drying. We conducted a pilot tolerability and safety study in 15 JC pollinosis patients who were exposed to 15 000 pollen grains/m³ for 2 h. Symptoms manifested on average 33 min after start of exposure. The subjects experienced no serious side-effects, and pollen exposure at 15 000 grains/m³ was confirmed safe. After exposure, the number of intranasal and intraocular pollen grains was 469 and 602, respectively. The lower number of pollen grains in the nose than in the eyes was considered due to sneezing and nasal discharge. Further studies are needed to clarify the number of pollen grains required for the occurrence of symptoms in the OHIO Chamber.