Study On The Relationship Of Macrophage Migration Inhibitory Factor(MIF)and NF-κB Signal Pathway In Steriod-resistant Asthma Patients

Objective: To explore the relationship of macrophage migration inhibitory factor(MIF)and NF-κB signal pathway in steriod-resistant asthma patients.Methods: Patients with asthma were recruited in the study,and those patients were divided into two groups,steroid resistant group(SRA)and steroid sensitive group(SSA)according to the diagnostic criteria.And healthy adults were recruited as control group.Peripheral venous blood were sampled and peripheral blood mononuclear cells(PBMCs)were separated.Plasma levels of MIF were measured by ELISA.Cytosolic NF-κB and IκB expression in PBMCs were determined by western bloting.The expression level of MIF m RNA was determined by Reverse Transcription-Polymerase Chain Reaction(RT-PCR).Results:The difference of FEV1%(△FEV1%,Forced expiratory volume in one second,FEV1predicted)of SRA group was significantly lower that that of SSA group(6.05±2.64 vs16.39±9.62,t=3.669,P≤0.001).The length of hospitalized day of SRA group was significantly longer that that of SSA group.Plasma MIF levels of SRA,SSA and controls were 104.03±15.15pg/ml,88.64±17.19 pg/ml,82.35±14.58 pg/ml,respectively,and the differences among three groups were significant(F=14.416,P<0.001).The level of IκB in SRA patients was significantly lower than SSA patients,and the levels of IκB in SRA and SSA patients was significantly lower than that of controls.higher in steroid-resistant patients compared with steroid-sensitive patients and controls.The levels of NF-κB in SRA and SSA patients was significantly higher than that of controls,while the difference of the level of NF-κB in SRA and SSA patients was not significant.The level of plasma MIF was negatively correlated with FEV1% in SRA patients(r=-0.622,P=0.023)and in SSA patients(r=-0.532,P=0.039).The level of plasma MIF was positively correlated with the level of IκB in SRA patients(r=-0.622,P=0.023).The level of MIF m RNA in PBMCs was positively correlated with the level of NF-κB in SRA patients(r=0.429,P=0.045).The level of plasma MIF was positively correlated with the level of NF-κB in SSA patients(r=0.498,P=0.036).The level of MIF m RNA in PBMCs was positively correlated with the level of NF-κB in SSA patients(r=0.682,P=0.002).Conclusion:The levels of plasma MIF and MIF m RNA expression were increased in SRA patients,which indicated that MIF may play a role in responsiveness to steroid therapy in asthma patients.The levels of plasma MIF was negatively correlated with the level of IκB and positively correlated with the level of NF-κB,which indicated that the NF-κB/IκB signaling pathway may play a role in steroid-resistant asthma.MIF may be a target for predicting responsiveness to steroid therapy in asthma patients,and even a potential target for steroid sparing for steroid resistant patients.