Protective effects of combined Mycobacterium bovis BCG and interleukin-12 vaccination on airway inflammation in a murine model of allergic asthma.
OBJECTIVE
Allergic asthma is characterized by chronic airway inflammation and airway hyperresponsiveness driven by allergen-specific T helper (Th)2 cells. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination has been documented to suppress Th2 responses and allergic airway inflammation in animal models. Since interleukin (IL)-12 is capable of inhibiting Th2 responses, we sought to investigate whether IL-12 could function as an adjuvant to increase the efficacy of BCG vaccination against allergic asthma.


METHODS
BALB/c neonatal mice (24 mice, 48-72 h old) were randomly divided into 3 subgroups (n = 8 for each group) to be immunized with PBS (control) or BCG with or without DNA plasmid-expressing IL-12. All of the mice were then sensitized and provoked with ovalbumin (OVA) to establish a model of allergic asthma.


RESULTS
Mice vaccinated with BCG alone showed a significant reduction in airway inflammation, percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and serum OVA-specific immunoglobulin E (IgE) levels in comparison with control animals. The suppressive effects of BCG were substantially augmented by the combination with IL-12. Furthermore, a decreased IL-4 and increased interferon-gamma (IFN-gamma) production in BAL fluid were observed in animals inoculated with BCG alone or with IL-12 relative to control animals.


CONCLUSIONS
Our data indicate that the combined vaccination with BCG and IL-12 yields a favorable outcome in prevention of experimental allergic airway inflammation, which is likely mediated through triggering a shift from a Th2 response to a Th1 response.
Ke
Xia
X
Department of Otolaryngology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
Huang
Jiangju
J
Chen
Quan
Q
Hong
Suling
S
Zhu
Daoyin
D
D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology*; D010047:Ovalbumin / Q000633:toxicity; D012137:Respiratory System / Q000187:drug effects
D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin