Propofol Inhibits Th2-type Asthma Inflammation Through GABA_A Receptor

Background:Propofol has been shown to attenuate airway hyperresponsiveness in asthma patients.Our previous study showed that it may alleviate lung inflammation in a mouse model of asthma.Given the critical role of T-helper cell type-2(Th2)differentiation,Th2 cell apoptosis resistances in asthma pathology and the immunomodulatory role of the gamma-aminobutyric acid type A(GABAA)receptor,we hypothesized that propofol could alleviate asthma inflammation by inhibiting Th2 cell differentiation via the GABAA receptor.The purpose of this research is to provide more evidence for the application of propofol on asthmatic airway inflammation besides its smooth muscle relaxing effect.Methods:First,we compared the success rate of intranasal challenge versus aerosol challenge.According to the comparison results,we utilized chicken ovalbumin-sensitized and intranasal challenged asthmatic mice for the following experiments.Propofol,GABAA receptor agonist muscimol and antagonist picrotoxin was given separately before intranasal challenge to observe the effect of propofol on Th2 type asmatic lung inflammation and determine if GABAA receptor activation is involved.For in vitro testing,we differentiated Th2 cell and intervened with propofol,muscimol and picrotoxin.Th2 cell type cytokines as well as the cell proliferation and apoptosis were measured to assess the effects of propofol on Th2 cell differentiation and determine the underlying mechanisms.To exclude the effect of adjuvant,we also did intralipid intervention.Results:Intranasal challenge demonstrated higher levels of general lung inflammation,expression of interleukin-4(IL-4)and signal transducer and activator 6(STAT6).We found that propofol significantly decreased inflammatory cell counts,interleukin-4 and inflammation score in vivo.Propofol,instead of intralipid,significantly reduced the Th2-type cytokine interleukin-5 secretion and caused Th2 cell apoptosis without obvious inhibition of proliferation in vitro.Muscimol simulated the effect of propofol,whereas pretreatment with reversed this effect,at least in partial.Conclusions:This study demonstrates that intranasal challenge is more effective than aerosol challenge.The anti-inflammatory effects of propofol on Th2-type asthma inflammation in mice are mediated by inducing apoptosis without compromising proliferation during Th2 cell differentiation via GABAA receptor activation.The adjuvant intralipid is not involved in the anti-inflammatory effect.