OBJECTIVESince human mast cell is an important source of cytokines, it is of importance to understand the effects of anti-allergic drugs on cytokines modulation in mast cells. In the present study, we aimed at observing whether IL-4 could be released from human mast cell line (HMC-1) after the stimulation of PMA + A23187, and the effects of systemic glucocorticosteroid, dexamethasone, topical glucocorticosteroid, budesonide and H1 antagonist, desloratadine on IL-4 release and mRNA expression.

METHODSHMC-1 was stimulated with 25 ng/ml phorbol 12-myristate 13-acetate (PMA) and 2.5 x 10(-7) mol/L ionomycin (A23187) and cultured for 6 hours, 12 hours and 24 hours respectively in the presence or absence of 10(-6)-10(-10) mol/L concentrations of test drugs. Culture supernatants were collected and the levels of IL-4 were assayed by enzyme-linked immunosorbent assays (ELISA). The mRNA expression of IL-4 was measured by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSHMC-1 expressed IL-4 mRNA and the resulting protein production of IL-4 released after being stimulated with PMA plus A23187. Dexamethasone, budesonide and desloratadine had potent inhibitory effect on IL-4 release at any concentrations and time points, with significant deference (P < 0.05) compared to the control cells. The inhibitory effect did not show time-dependent and concentration-dependent manner. Desloratadine and budesonide showed neither up-regulatory nor down-regulatory effects on IL-4 mRNA expression at the test concentrations, however, desloratadine could down-regulate IL-4 mRNA expression.

CONCLUSIONSHMC-1 could express and produce IL4 after stimulation. Dexamethasone, budesonide and desloratadine all had inhibitory effects on IL-4 release from HMC-1. In addition, desloratadine could also inhibit the IL-4 mRNA expression.

Budesonide ; pharmacology ; Cell Line ; Dexamethasone ; pharmacology ; Humans ; Interleukin-4 ; biosynthesis ; Loratadine ; analogs & derivatives ; pharmacology ; Mast Cells ; drug effects ; metabolism ; Tetradecanoylphorbol Acetate ; pharmacology

OBJECTIVETo observe the early and late symptomatic, pathological and immunological changes in an intranasal ovalbumin-induced animal model of allergic rhinitis in guinea pigs.

METHODSGuinea pigs were intranasally sensitized with ovalbumin absorbed on aluminum hydroxide and after 5 days' interval, they were challenged with 1% ovalbumin solution once every 3 days for total 11 times. Two control groups were studied in parallel, the positive treatment control group was treated with antihistamine and the negative control group was sham-sensitized and sham-challenged. Typical symptoms of allergic rhinitis, such as sneezing, nasal scratching, nasal blockage and rhinorrhea were evaluated. Passive cutaneous anaphylaxis reaction (PCA) was performed to measure the levels of IgG1 and IgE. Eosinophils infiltration and goblet cells in nasal mucosa were observed. In addition, the level of histamine and the number of total leukocytes and eosinophils in the nasal lavage fluid were also measured.

RESULTSIn the model group, symptoms of sneezing, nasal scratching, nasal blockage and rhinorrhea were induced after ovalbumin challenge. The respiratory rate (RR), which reflected the resistance of upper airway, showed a biphasic change. In the PCA test, IgG1 and IgE levels increased after challenges. Eosinophil infiltration in nasal mucosa was more obvious in active groups in comparison to with the negative control group (P < 0.05 or < 0.01). The histamine, total leucocytes and eosinophils levels in nasal lavage fluid also showed higher in the model group (P < 0.05 or < 0.01). The antihistamine treated animals were also induced out above changes but modest compared with the model group (P < 0.05 or < 0.01). The negative control showed few of above changes with significant difference (P < 0.05 or < 0.01).

CONCLUSIONSOur results implied that the modified animal model of allergic rhinitis was capable of showing satisfactory symptomatic and pathophysiological changes in allergic rhinitis. It showed a biphasic nasal blockage with shorter establishment duration. The model also had good treatment reaction to antihistamine. The animal model we introduced may be useful in the study of allergic rhinitis.

Administration, Intranasal ; Animals ; Disease Models, Animal ; Guinea Pigs ; Nasal Lavage Fluid ; Ovalbumin ; administration & dosage ; Rhinitis, Allergic, Perennial