Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 131, Issue 2, Pages 199-205Publisher
WILEY
DOI: 10.1046/j.1365-2249.2003.02073.x
Keywords
interleukin-12; asthma; CD4 T cell; apoptosis
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Funding
- NHLBI NIH HHS [R01 HL061005, P01 HL036577, HL-36577, HL-61005] Funding Source: Medline
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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.
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