Therapeutic effects of recombinant human interleukin-1 receptor antagonist on toluene-2,4-diisocyanate-induced guinea pig allergic rhinitis model / 国际药学研究杂志

ABSTRACT

Objective To evaluate the effects of the recombinant human interleukin-1 receptor antagonist(rhIL-1ra)on a tol?uene-2,4-diisocyanate(TDI)-induced guinea pig allergic rhinitis (AR)model. Methods An AR model was established via sensiti?zation and challenge of two-step procedure using TDI in guinea pigs. Normal animals were treated only with the olive oil(TDI vehicle). Sixty adult guinea pigs were randomly divided into six groups(n=10)normal group,model group(rhIL-1ra vehicle),positive con?trol group(budesonide,25.6μg/kg),rhIL-1ra treated groups(rhIL-1ra 50,100 and 200μg/kg,respectively). From day 8 after sensi?tization,animals of all the groups were treated respectively with the agents or vehicle once a day for 14 days. During the observation pe?riod,the index of clinic score was recorded for every animal. At day 14 of the dosing,guinea pigs were sacrificed 30 min after the last TDI challenge and observation. Blood samples were taken from the abdominal aorta to prepare the serum for detection of histamine , and the nasal mucosase were dissected for histamine detection and histopathological observation. Results Compared with the guinea pigs in normal group,those in the model group exerted the typical symptoms of AR. It was shown that rhIL-1ra could improve nasal symptoms and cause a significant decrease in the instances of nasal sneezing as well. In addition,rhIL-1ra significantly reduced the concentrations of histamine in the nasal mucosa and IgE in the blood compared with those in the model group(P<0.05). Moreover, the pathological results showed that less edema,vasodilation and inflammatory cell infiltration were found in the nasal mucosa after rhIL-1ra application. Budesonide also showed the above effects with no significant difference compared with rhIL-1ra. Conclusion A guinea pig allergic rhinitis model is successfully induced by TDI. The results indicated that rhIL-1ra(50-200μg/kg)is effective in im?proving allergic rhinitis. Our findings indicated that rhIL-1ra might serve as a potential new drug for allergic rhinitis therapy.