[Effects of interleukin 1 receptor antagonist on allergy asthma in rat model and its mechanism].
OBJECTIVE
To study the effects of interleukin 1 receptor antagonist (IL-Ira) on allergy asthma and its mechanism.


METHODS
Thirty female SD rats underwent intraperitoneal and hypodermic injection of ovalbumin (OVA) on days 1 and 14, and then underwent spraying of OVA aerosol since day 21 for 7 days so as to provoke asthma, and then the rats were randomly divided into 3 equal groups: asthma model group, low dose IL-1ra treatment group undergoing intravenous injection of IL-1ra 6 mg/kg before each provocation (low dose treatment group), and high dose IL-1ra treatment group undergoing intravenous injection of IL-1ra 30 mg/kg before each provocation (high dose treatment group). Another 10 rats were used as normal controls. Twenty-four hours after the last provocation physiological monitoring equipment was used to detect the pulmonary function. Then the rats were killed. Bronchoalveolar lavage fluid (BALF) was collected. ELISA was used to detect the serum IgE content. The ratio of inflammatory cells from the BALF was calculated. Microscopy was conducted to observe the histopathology of lung. RT-PCR was used to examine the mRNA expression of NF-kappaB and signal transducer and activator of the transcription 6 (STAT6).


RESULTS
The respiratory rate, expiratory flow, percentage of eosinophils in BALF inflammatory cells, peripheral blood IgE concentration, mRNA expression of STAT6 and NF-kappaB of the asthma group were (206 +/- 11) times/min, (77 +/- 8) microl/s, 24.8% +/- 1.3%, (72.5 +/- 8.1) ng/ml, 0.294 +/- 0.048, and 0.686 +/- 0.052 respectively, all significantly higher than those of the low dose treatment group [(183 +/- 9) times/min, (64 +/- 5) microl/s, 18.5% +/- 3.1%, (63.4 +/- 4.8) ng/ml, 0.229 +/- 0.038, and 0.613 +/- 0.062 respectively, all P < 0.05] and those of the high dose treatment group [(181 +/- 11) times/min, (57 +/- 4) microl/s, 14.7% +/- 2.1%, (41.4 +/- 7.4) ng/ml, 0.194 +/- 0.076, and 0.352 +/- 0.267, all P < 0.05]. The therapeutic effect of high dose treatment group is superior to that of low dose treatment group (P < 0.05).


CONCLUSIONS
IL-1ra is significantly effective in treatment of allergic asthma, and its potential mechanism is through regulating both STAT6 mRNA and NF-kappaB mRNA expression simultaneously.
Liu
Zhong-Cheng
ZC
College of Pharmacy, Hebei University, Baoding 071002, China.
Wang
Yuan-Yuan
YY
Zou
Min-Ji
MJ
Wang
Jia-Xi
JX
Xu
Dong-Gang
DG
D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000150:complications; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D016328:NF-kappa B / Q000096:biosynthesis; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000096:biosynthesis
D053590:Interleukin 1 Receptor Antagonist Protein; D016328:NF-kappa B; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor