Effects of post-inhalation treatment with interleukin-12 on airway hyper-reactivity, eosinophilia and interleukin-18 receptor expression in a mouse model of asthma.

Abstract

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-18Ralpha (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.

• Authors: K Kuribayashi, T Kodama, H Okamura, M Sugita, T Matsuyama
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 32 Issue 4 Pg. 641-9 (Apr 2002) ISSN: 0954-7894 [Print] England
• PMID: 11972614 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Il18r1 protein, mouse
• Interleukin-18 Receptor alpha Subunit
• Receptors, Interleukin
• Receptors, Interleukin-18
• Interleukin-12
• Immunoglobulin E
• Ovalbumin

Topics

• Administration, Inhalation
• Animals
• Asthma (drug therapy, immunology, pathology)
• Bronchial Hyperreactivity (drug therapy, immunology, pathology)
• Bronchoalveolar Lavage Fluid (cytology, immunology)
• Cytokines (metabolism)
• Immunoglobulin E (blood)
• Interleukin-12 (administration & dosage, pharmacology, therapeutic use)
• Interleukin-18 Receptor alpha Subunit
• Lung (pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Ovalbumin (immunology)
• Pulmonary Eosinophilia (drug therapy, immunology, pathology)
• Receptors, Interleukin (metabolism)
• Receptors, Interleukin-18