Bacillus Calmette-Guérin-induced interleukin-12 did not additionally improve clinical and immunologic parameters in asthmatic children treated with sublingual immunotherapy.
OBJECTIVE
To evaluate the effect of bacillus Calmette-Guérin (BCG) as an adjuvant to specific sublingual immunotherapy (SLIT) on the cytokine profile of peripheral blood mononuclear cells (PBMCs) and clinical outcome.


METHODS
Thirty-two children with asthma and rhinitis allergic to house dust mite (HDM) with negative purified protein derivative (PPD) skin test response were enrolled. After a run-in period of 8 weeks, patients were randomized to receive either SLIT only (n=16) or one dose of BCG immunization before initiation of SLIT (n=16) with a standardized Dermatophagoides pteronyssinus (D. pteronyssinus)+D. farinea 50/50 extract. PPD-negative asthmatics (n=5) allergic to HDM receiving inhaled therapy only were included for comparison of cytokine levels in PBMC cultures. Efficacy was assessed both at the end of run-in and 6 months of treatment periods with criteria including symptom, medication and quality-of-life (QoL) scores, IgE levels, lung function, provocation concentration (PC20), eosinophil count and skin prick tests. IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-gamma levels were determined in antigen specifically and polyclonally stimulated PBMC cultures.


RESULTS
Both treatment groups showed significant improvement at the end of 6 months for asthma and rhinitis scores and QoL, number of asthma attacks, amount of beta2-agonists, inhaled and intranasal steroids, blood eosinophil counts and PC20. Interestingly, phytohaemagglutinin (PHA)-stimulated IL-12 and D. pteronyssinus-stimulated IFN-gamma in PBMC were significantly higher in the treatment groups than controls. In addition, IL-12 levels in response to D. pteronyssinus and PHA stimulation were significantly higher in the SLIT+BCG group than the SLIT alone group and controls.


CONCLUSIONS
The present study demonstrates that successful SLIT is parallel to increased IFN-gamma production by PBMC. Although simultaneous BCG vaccination enhanced IL-12 production, it did not additionally improve the clinical outcome.
Marmara University Hospital, Pediatric Allergy and Immunology Division, Istanbul, Turkey.
C
C
Arikan
N N
NN
Bahceciler
G
G
Deniz
M
M
Akdis
T
T
Akkoc
C A
CA
Akdis
I B
IB
Barlan
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000286:Administration, Sublingual; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D001500:BCG Vaccine / Q000008:administration & dosage*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology*; D007958:Leukocyte Count; D008297:Male; D012220:Rhinitis / Q000276:immunology / Q000628:therapy; D012882:Skin Tests; D018709:Statistics, Nonparametric; D017211:Treatment Failure
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D018664:Interleukin-12; D007371:Interferon-gamma