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Effects of post‐inhalation treatment with interleukin‐12 on airway hyper‐reactivity, eosinophilia and interleukin‐18 receptor expression in a mouse model of asthma
Author(s) -
Kuribayashi K,
Kodama T,
Okamura H,
Sugita M,
Matsuyama T
Publication year - 2002
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.0954-7894.2002.01346.x
Subject(s) - ovalbumin , eosinophilia , immunology , immunoglobulin e , medicine , interleukin 5 , cytokine , antigen , interleukin , antibody
Summary Background Correcting Th1/Th2 imbalance with administration of IL‐12 before and during antigen challenge holds therapeutic promise in asthma. However, the effects of IL‐12 on the established asthmatic responses have not fully been examined. Objective We investigated whether IL‐12 administered after antigen challenge could diminish airway hyper‐reactivity (AHR) and eosinophilia in mice actively sensitized to ovalbumin. We also have investigated the ability of administered IL‐12 to induce IL‐18 receptor (IL‐18R) expression that may lead possible synergic action of IL‐12 with endogenous IL‐18. Methods C57BL/6 mice immunized to ovalbumin (OVA) by intraperitoneal (i.p.) injection, were challenged three times with an aerosol of OVA every second day for 8 days. Recombinant IL‐12 (500 ng) was intravenously administered on a single occasion 1 h after the final challenge of mice. Mice were analysed for effects of IL‐12 on AHR, inflammatory cell infiltration and cytokine levels in lung tissue as well as serum immunoglobulin (Ig) E levels. Immunohistochemistry for IL‐18R was performed using rat monoclonal antibody specific for murine IL‐18Rα (IL‐1 receptor related protein; IL‐1Rrp). Results An intravenous IL‐12 administration diminished AHR, pulmonary eosinophilia and T lymphocyte infiltration, serum IgE, IL‐4 and IL‐13 in lung tissue. Expression of IL‐18R was induced in the mononuclear cells in the lung of mice exposed to OVA. IL‐12 administration enhanced the IL‐18R expression compared with the control. Conclusion These data indicate that IL‐12 can attenuate established antigen‐induced AHR and inflammation. In this mechanism it would be interpreted as follows: IL‐12 administration in OVA‐challenged mice decreased IL‐4 production and IgE production thereafter through direct effect on inhibiting the activation of established Th2 cells response and also combined effect with up‐regulation of IL‐18R expression by inflammatory cells in the lung.