Interleukin-12 inhibits antigen-induced airway hyperresponsiveness in mice.
The airway inflammation observed in allergic asthma is thought to be orchestrated by an antigen-driven T-helper-2 (Th2) lymphocyte response. In vitro data indicate that the presence of interleukin-12 (IL-12) during the primary stimulation of T-lymphocytes with antigen favors the development of Th1 cells. The aim of the present study was to examine the effect of IL-12 in vivo on antigen-induced airway changes in a murine model. C57BL/6 mice were actively sensitized to ovalbumin; 14 d later, they were exposed daily for 7 d to aerosolized ovalbumin. This resulted in airway eosinophilia, production of ovalbumin-specific IgE, and airway hyperresponsiveness to carbachol. Administration of recombinant murine IL-12 (rmIL-12) during the active immunization prevented these antigen-induced changes. In contrast, administration of rmIL-12 to actively immunized mice during the daily aerosol exposure (but not at the time of immunization) abolished airway eosinophilia and hyperresponsiveness without influencing the production of specific IgE. These results suggest that IL-12 can suppress antigen-induced airway changes despite the presence of circulating specific IgE.
Kips
J C
JC
Department of Respiratory Diseases, University Hospital Ghent, Belgium.
Brusselle
G J
GJ
Joos
G F
GF
Peleman
R A
RA
Tavernier
J H
JH
Devos
R R
RR
Pauwels
R A
RA
D000818:Animals; D000941:Antigens / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002217:Carbachol / Q000494:pharmacology; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000502:physiology*; D007378:Interleukins / Q000032:analysis; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000941:Antigens; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma; D002217:Carbachol; D010047:Ovalbumin