Effects Of Dexamethasone,Methylprednisolone And Roxithromycin On The Balance Of T_H1/T_H2 In Peripheral Blood Mononuclear Cells From Asthmatic Children In Vitro

Objectives Bronchial asthma in childhood is a common airway inflammatory disease. There are evidences that the incidence of asthma in children tend to ascend in recent years, which threatened badly the health of athmatic children. Glucocoticoids make an important role in the clinical therapy to asthma. We found that Methylprednisolone is more efficient to treat asthma in children than that of dexamethasone. In the study, the effects of methylprednisolone (MP) and dexamethasone (DEX) on production in vitro of Th1/Th2 cytokines by PBMC from asthmatic children were observed comparatively. Macrolide antibiotics (e.g. erythromycin and roxithromycin) are common antibacterial agents. It is reported recently that macrolide antibiotics may regulate the imbalance of Th1/Th2 existed in asthmatic patients. In this study, the effects of marolide antibiotic roxithromycin (RXM) on the Th1/Th2 cytokines production in vitro was measured to make sure it could be used as an immune regulator in therepy of asthma.Methods 15 asthmatic children and 14 healthy age matched volunteers were included, whose PBMCs were isolated and cultured for 48 hours in the presence ofvarious concentrations of DEX, MP and RXM. Then IFNγ, IL-4, IL-10 and IL-12 activities in culture supernatants were assayed using commercially available human cytokine enzyme-linked immunosorbent assay test kits (ELISA kits), and the expression of IFNγ and IL-4mRNA was detected by reverse transcription polymerase chain reaction.Results1. IL-4 production, expression of IL-4 mRNA, and the ratio of IFNγ/IL-4 were higher in asthmatic children comparing to healthy children.But the secretion of IFNγ was not different between asthmatic and healthy children. IL-10 production in asthmatic children tends to ascend. DEX and MP were capable of inhibiting the production of IFNγ, IL-4 and IL-12 by PBMC from healthy children, but not IL-10.2. DEX and MP were able to inhibit the secretion of IFNγ, IL-4, IL-12 and expression of IFNγand IL-4 mRNA as well. MP could enhance the ratio of IFNγ/IL-4, while DEX and MP both had no effects on IL-10.3. 50μg/ml RXM could promote the expression of IFNγmRNA, and increase the secretion of IFNγand IL-12 by PBMC from asthmatic children with enhancing the ratio of IFNγ/IL-4. Moreover, it tended to increase the production of IL-10, while 5μg/ml RXM had no effects on the secretion of IFNγ, IL-4, IL-10, IL-12 and the ratio of IFNγ/IL-4 in asthmatic children, so did 5μg/ml and 50μg/ml RXM .Conclusions1. DEX and MP could inhibit statistically the expression of IFNγand IL-4 mRNA and the secretion of IFNγ, IL-4 and IL-12. MP could be used as a regulator to restore the balance of Th1/Th2 cytokine production.2. 50μg/ml RXM could strengthen the expression of IFNγmRNA, and promote the secretion of IFNγand IL-12. Therefore, it could restore the balance of Th1/Th2 cytokines production. Additionally, it tended to promote PBMC from asthmatic children to secret IL-10 in vitro.The data in this study show that MP could positively regulate the production of3. Th1/Th2 cytokines by PBMC from asthmatic children, consistent with clinical observation. It is likely that MP will be an option in the therapy of asthma. Meanwhile, higher concentration of RXM in a safe scale may be used as a regulator to restore the balance of Th1/Th2 cytokine production.