Effects of post-inhalation treatment with interleukin-12 on airway hyper-reactivity, eosinophilia and interleukin-18 receptor expression in a mouse model of asthma
Article first published online: 21 NOV 2002
Clinical & Experimental Allergy
Volume 32, Issue 4, pages 641–649, April 2002
How to Cite
Kuribayashi, K., Kodama, T., Okamura, H., Sugita, M. and Matsuyama, T. (2002), Effects of post-inhalation treatment with interleukin-12 on airway hyper-reactivity, eosinophilia and interleukin-18 receptor expression in a mouse model of asthma. Clinical & Experimental Allergy, 32: 641–649. doi: 10.1046/j.0954-7894.2002.01346.x
- Issue published online: 21 NOV 2002
- Article first published online: 21 NOV 2002
- Submitted 6 February 2001; revised 7 September 2001; accepted 1 October 2001
- bronchial asthma;
- interferon-γ interleukin-12;
- interleukin-18 receptor;
- Th2 balance
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.