Recombinant Mycobacterium bovis BCG producing IL-18 reduces IL-5 production and bronchoalveolar eosinophilia induced by an allergic reaction

Allergy. 2005 Aug;60(8):1065-72. doi: 10.1111/j.1398-9995.2005.00826.x.


Background: Allergic reactions occur through the exacerbated induction of a Th2 cell type expression profile and can be prevented by agents favoring a Th1 profile. Bacillus Calmette-Guérin (BCG) is able to induce high IFN-gamma levels and has been shown to decrease experimentally induced allergy. The induction of IFN-gamma is mediated by interleukin (IL)-12 known to be secreted upon mycobacterial infections and can be enhanced by IL-18 acting in synergy with IL-12.

Objective: We evaluated the ability of a recombinant BCG strain producing IL-18 (rBCG) to modify the Th2 type responses in a murine model of ovalbumin (OVA)-dependent allergic reaction.

Methods: Mice were injected intraperitoneally or intranasally with OVA at days 0 and 15 and exposed to an OVA aerosol challenge at days 29, 30, 31 and 34. At days 0 and 15, two additional groups of mice received OVA together with 5 x 10(6) colony forming units of either rBCG or nonrecombinant BCG.

Results: A time-course analysis of OVA-specific immunoglobulin (Ig)E, IgG1 and IgG2a levels indicated no significant difference between the three groups of mice. However, following in vitro stimulation with OVA, lymph node cells from rBCG-treated mice produced less IL-5 and more IFN-gamma than those of mice injected with nonrecombinant BCG. In addition, 48 h after the last OVA challenge, a strong reduction of bronchoalveolar eosinophilia was found in the rBCG-injected mice compared to the nontreated or nonrecombinant BCG-treated groups.

Conclusion: These results indicate that the production of IL-18 by rBCG may enhance the immunomodulatory properties of BCG that suppress pulmonary Th2 responses and, in particular, decrease airway eosinophilia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BCG Vaccine / metabolism*
  • Bronchi / pathology*
  • Eosinophilia / etiology
  • Eosinophilia / prevention & control*
  • Female
  • Hypersensitivity / complications*
  • Interleukin-18 / biosynthesis*
  • Interleukin-5 / antagonists & inhibitors*
  • Interleukin-5 / biosynthesis
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Pulmonary Alveoli / pathology*
  • Vaccines, Synthetic / metabolism


  • BCG Vaccine
  • Interleukin-18
  • Interleukin-5
  • Vaccines, Synthetic