Adenovirus-Mediated IL-10 Gene for the Treatment of Autoimmune Inner Ear Disease-an Experimental Study

ABSTRACT

Objective To evaluate therapeutic effects of transferring recombinant replication -defective ade‐novirus vector of interleukin 10(IL -10) gene into inner ear of guinea pig for the treatment of autoimmune inner ear disease .Methods The conspecific crude inner ear antigens (CIEAgs) were prepared and used to immunize guinea pigs with Freund's adjuvant that resulted autoimmune inner ear diseases (AIED) in 20 animals .Then they were ran‐domly divided into three groups .Through the way of round window membrane micro -injection ,adenovirus vector containing IL -10(Ad -IL -10) gene were implanted in group A(ten animals) ,recombinant adenovirus with yellow fluorescent protein(Ad -EYFP) marked was implanted in group B(five animals) ,and artificial perilymph were implanted in group C( five animals) .Seven days later ,auditory brain-stem response (ABR) thresholds were determined ,the guinea pig inner ears were obtained ,and the immunohistochemistry staining were perform for detec‐ting adenovirus vector transfection with immunofluorescence and the gene product interleukin 10 expressions with enzyme immunohistochemistry .Results Immunohistochemistry staining showed that the adenovirus carrying IL -10 gene could transfer the psalterial cord ,spiral ligament ,Corti organ ,spiral ganglion ,cochlear axis vessels and co‐chlear bone paries .It could generate gene product (IL -10 ) in same sites .The mean ABR thresholds were increased in each group after modeling .The differences were statistically significant .After injection of the inner ear ,the mean ABR thresholds of group A were lower than those of group B and group C .The light microscopic revealed the im‐munological inflammatory response were lighter than in group B and group C .Conclusion The adenovirus could transfer IL -10 gene into inner ear of guinea pig and express its products in many parts of inner ear .The immunity regulating gene can reduce the immunity damage and hearing functional impairment .