The Effect Of Neonatal Pneumococcal Pneumonia On Vitamin A Status And Its Relationship With Pulmonary Immunity And Airway Responsiveness

Objective:To investigate the effect of neonatal streptococcus pneumoniae pneumoniae(S.pp)on vitamin A status and its relationship with pulmonary immunity and airway responsiveness.Methods:Neonatal(1-week-old)BALB/c mice were infected intranasally in conscious with 2×10~7 CFU of S.pneumoniae(D39)in 5ul of PBS,mock-infected mice were intranasally with 5ul of PBS,the vitamin A supplementation mice were administrated orally with a dose of 20IU/g of VA for four consecutive days,the other two groups gave the same dose of VA dissolved solute(rapeseed oil).To determine the effect of neonatal S.pp on vitamin A status in mice,we monitored vitamin A levels in lung,serum,and liver on 7,14,21,28 days post infection by HPLC.Five weeks after infection,lung tissue slices were made and stained with H&E to observe the lung pathology.Airway hyperresponsiveness(AHR)was measured in conscious,unrestrained mice by means of whole-body plethysmography.The levels of IL-4,IL-5,IL-13,IL-17A and IFN-γin BALF were examined with enzyme-linked immunosorbent assay(ELISA);and the levels of Th1,Th2 and Foxp3~+Treg cells were determined by flow cytometry.Results:Here we found that after neonatal S.pp,the VA status in lung decreased to the fourth week after infection,and the serum VA decreased until the 14th day after infection,while the VA level in the liver was not statistically significant.The lung inflammatory cells infiltration in vitamin A supplementation group was significantly more intensive than that in neonatal S.pp group.Our data also showed that concentration of IFN-γin BALF of vitamin A supplementation group was significantly higher than that in the neonatal S.pp group(P<0.01),while concentrations of IL-4,IL-5,IL-13 and IL-17A were significantly lower(P<0,05).Th1 and Foxp3~+Treg cells were significant higher in vitamin A supplementation group as compared with the neonatal S.pp group(P<0.01),while Th2 cells in vitamin A supplementation group were significantly lower than that in the neonatal S.pp group(P<0.01).Thus,the ratio of Th1/Th2,Th1/Th17 and Foxp3~+Treg/Th17wassignificantlyincreasedinvitaminA supplementation group than that in the neonatal S.pp group(P<0.01).We also found that airway hyperresponsiveness in vitamin A supplementation was significantly lower than that in the neonatal S.pp group(P<0.001).Conclusion:Therefore,neonatal S.pp decreased lung VA significantly,supplementation of VA after neonatal S.pp can reduce lung inflammatory cells infiltration,improve the expression of Th1 and Foxp3~+Treg cells in lung,correcttheimbalanceofTh1/Th2,Th1/Th17and Foxp3~+Treg/Th17and inhibit the formation of airway hyperresponsiveness.