Role Of Vitamin A In Neonatal Streptococcus Pneumoniae Pneumonia-induced Aggravation Of Asthma In Mice

Objective : To study the role of vitamin A(VA)in neonatal streptococcus pneumoniae pneumonia(S.pp)-induced adulthood asthma and to clarify that whether neonatal S.pp aggravated asthma via lowering VA level,and whether VA supplementation after neonatal S.pp would inhibit the aggravation.Methods:The neonatal BALB/c mice(6-8day)were randomly divided into control group(Con group)、 S.pp group and VA supplementation following neonatal S.pp group(S.pp+VA group).The OVA allergic asthma models were built 3 weeks(4 weeks old)after neonatal S.pp,mice were then divided into Con group,OVA group,S.pp+OVA group,and S.pp+VA+OVA group respectively.We firstly monitored the effect of neonatal S.pp on VA levels in serum,liver and lung by HPLC.The lung pathology changes,AHR,lung inflammatory infiltration,CD4+T cell subtypes and cytokines were compared among the four groups.We finally detected the effect of neonatal S.pp and effect of VA supplementation following neonatal S.pp on STAT4 total protein expression and its phosphorylated level.Results: Neonatal S.pp resulted significantly in continuous decrease of VA till to the 4th week post neonatal S.pp.VA supplementation after neonatal S.pp alleviated dramatically lung pathology changes,AHR and inflammatory cells infiltration in asthmatic model.VA supplementation induced prominently Th1,Foxp3+Treg cells differentiation and promoted strikingly STAT4 activation,whereas inhibited Th2 cell differentiation.There was no significant effect of VA supplementation on Th17 cell differentiation and STAT4 total protein expression.Conclusion: VA supplementation after neonatal S.pp inhibits S.pp-induced aggravation of asthma,and may be related to VA-induced enhancement of STAT4 phosphorylation and ensuing effect on CD4+T cell differentiation.