Counterbalancing of TH2-driven allergic airway inflammation by IL-12 does not require IL-10

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:107

Article

Tournoy, KG ; Kips, JC ; Pauwels, RA

关键词: IL-10;    IL-12;    allergen;    airway inflammation;    airway responsiveness;    T(H)1;    T(H)2;    eosinophil;    IgE;    asthma;   

DOI  :  10.1067/mai.2001.112693

来源: Elsevier

【 摘 要 】

Background: Asthma is characterized by allergen-induced airway inflammation orchestrated by T(H)2 cells. The T(H)1-promoting cytokine IL-12 is capable of inhibiting the T(H)2-driven allergen-induced airway changes in mice and is therefore regarded as an interesting strategy for treating asthma. Objective: The antiallergic effects of IL-12 are only partially dependent of IFN-gamma, Because IL-12 is a potent inducer of the anti-inflammatory cytokine IL-10, the aim of the present study was to investigate in vivo whether the antiallergic effects of IL-12 are mediated through IL-10. Methods: C57BL/6J-IL-10 knock-out IL-10(-/-)) mice were sensitized intraperitoneally to ovalbumin (OVA) and subsequently exposed from day 14 to day 21 to aerosolized OVA (1%). IL-12 was administered intraperitoneally during sensitization, subsequent OVA exposure, or both. Results: IL-12 inhibited the OVA-induced airway eosinophilia, despite the absence of IL-10. Moreover, a shift from a T(H)2 inflammatory pattern toward a T(H)1 reaction was observed, with concomitant pronounced mononuclear peribronchial inflammation after IL-12 treatment. Allergen-specific IgE synthesis was completely suppressed only when IL-12 was administered along with the allergen sensitization. Furthermore, treating the animals with IL-12 at the time of the secondary allergen challenge resulted not only in a significant suppression of the airway responsiveness but also in an important IFN-gamma -associated toxicity. Conclusions: These results indicate that IL-12 is able to inhibit allergen-induced airway changes, even in the absence of IL-10, In addition, our results raise concerns regarding the redirection of T(H)2 inflammation by T(H)1-inducing therapies because treatment with IL-12 resulted not only in a disappearance of the T(H)2 inflammation but also in a T(H)1-driven inflammatory pulmonary pathology.

【 授权许可】

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