Role of interleukin-12 in the regulation of CD4+ T cell apoptosis in a mouse model of asthma.

Abstract

Allergic asthma, a chronic inflammatory disease of the airways, is characterized by the presence of T helper 2 cells and eosinophils in sputum, bronchoalveolar lavage, and mucosal biopsy specimens. Although the T helper 1-promoting cytokine, interleukin-12, is capable of inhibiting the T helper 2-driven asthma symptoms and bronchial responsiveness, the specific mechanisms underlying these interleukin-12 actions are unclear. The anti-allergic response to interleukin-12 is only partially dependent on interferon-gamma, which induces apoptosis by enhancing expression of Fas antigen. We therefore investigated in vivo whether the anti-allergic action of interleukin-12 is mediated through induction of apoptosis. C57BL/6 mice immunized to ovalbumin by intraperitoneal injection were challenged three times with an ovalbumin aerosol every second day for 7 days. Recombinant interleukin-12 was administered intravenously after the final challenge. After the last ovalbumin challenge, mice were examined for effects of interleukin-12 on inflammatory cell infiltration and apoptosis in the lung as detected by terminal deoxynucleotidyl transferase-mediated deoxyribonucleoside triphosphate nick end-labelling. Administration of interleukin-12 reduced ovalbumin-induced pulmonary eosinophilia (P < 0.01) and CD4+ T cell infiltration (P < 0.01). Moreover, treatment with interleukin-12 shortly after ovalbumin inhalation resulted in both increased interferon-gamma production (P < 0.01) and enhanced apoptosis of CD4+ T cells in allergic airway infiltrates (P < 0.05). These results suggest that the beneficial effects of interleukin-12 in asthma may include enhancement of apoptosis of CD4+ T cells in airways.

• Authors: T Kodama, K Kuribayashi, H Nakamura, M Fujita, T Fujita, K Takeda, A Dakhama, E W Gelfand, T Matsuyama, O Kitada
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 131 Issue 2 Pg. 199-205 (Feb 2003) ISSN: 0009-9104 [Print] England
• PMID: 12562378 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Recombinant Proteins
• Interleukin-12
• Interferon-gamma
• Ovalbumin

Topics

• Animals
• Apoptosis (drug effects, immunology)
• Asthma (immunology, pathology, prevention & control)
• CD4-Positive T-Lymphocytes (immunology, pathology)
• Disease Models, Animal
• Interferon-gamma (biosynthesis)
• Interleukin-12 (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Ovalbumin (immunology)
• Pulmonary Eosinophilia (prevention & control)
• Recombinant Proteins (pharmacology)