[Combined effects of neonatal Bacillus Calmette-Guerin vaccination and respiratory syncytial infection on experimental asthma in mice].
OBJECTIVE
Neonatal Bacillus Calmette-Guerin (BCG) vaccination could decrease asthma prevalence in human according to "hygiene hypothesis". The authors proposed a hypothesis that effect of BCG vaccination on inhibiting asthma in human might be reversed by respiratory virus infection. The objective of this study was to observe combined effects of neonatal BCG vaccination and respiratory syncytial virus (RSV) infection on experimental asthma in mice.


METHODS
Neonatal BALB/c mice were divided into five groups. Control and ovalbumin (OVA) groups were mock-vaccinated at birth and mock-infected at 3 weeks of age. BCG + OVA group was BCG-vaccinated and mock-infected. RSV + OVA group was mock-vaccinated and RSV-infected. BCG + RSV + OVA group was BCG-vaccinated and RSV-infected. Except for control group, all the other groups underwent ovalbumin (OVA) sensitization and challenge. Airway responsiveness to inhaled methacholine was measured and bronchoalveolar lavage (BAL) was performed after the last challege. Cells in BAL fluid (BALF) were counted. Cytokines in BALF and serum OVA-specific IgE were detected by ELISA and inflammatory characteristics of lungs was scored by staining with hematoxylin and eosin.


RESULTS
(1) The numbers of total white cells, lymphocytes, monocytes, neutrophils, and eosinophils in the BALF from all OVA-sensitized/challenged groups were significantly greater than those in control (P < 0.01), and BCG + OVA group had significantly lower total white cells, lymphocytes and eosinophils as compared with other OVA-sensitized/challenged groups (P < 0.05 or 0.01). (2) All OVA-sensitized/challenged groups had significantly lower IFNgamma (P < 0.05) and higher IL-4 (P < 0.05) level in BALF as compared with control, but there was no significant difference among all OVA sensitized/challenged groups. There was no significant difference in IL-10 level between all experimental groups. (3) All OVA-sensitized/challenged groups showed significantly higher serum OVA-specific IgE titers than control (P < 0.05 or 0.01), but no significant difference was found among all OVA sensitized/challenged groups. (4) RSV + OVA and BCG + RSV + OVA groups displayed the highest airway resistance and subsequently in order as follows: OVA group, BCG + OVA group and control group in severity of airway hyperreactivity (AHR), but no significant difference was found between RSV + OVA and BCG + RSV + OVA groups. (5) Histological score of peribronchiolitis, perivasculitis, alveolitis, and peribronchial eosinophilia in all OVA-sensitized/challenged groups was significantly higher than that in control. BCG + OVA group had significantly milder peribronchiolitis and peribronchial eosinophilia than the other OVA-sensitized/challenged groups (P < 0.05) and significantly milder alveolitis than OVA and BCG + RSV + OVA groups (P < 0.05).


CONCLUSIONS
Neonatal BCG vaccination decreased asthmatic inflammation and AHR and RSV infection could reverse anti-asthma effect of neonatal BCG vaccination in OVA-sensitized/challenged mouse model.
Li
Rui
R
Department of Clinical Immunology, Children's Hospital Affiliated to Chongqing University of Medical Sciences, Chongqing 400014, China.
Liu
En-mei
EM
Yang
Xi-qiang
XQ
Wang
Li-jia
LJ
D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000032:analysis / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D016753:Interleukin-10 / Q000032:analysis / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000472:pathogenicity; D016896:Treatment Outcome
D001500:BCG Vaccine; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin