Increased expression of interleukin-4 during liver allograft rejection.
OBJECTIVE
To investigate the respective roles of interleukin-2 (IL-2) and IL-4 during rejection, we evaluated the expression of IL-2, IL-2 receptor and IL-4 in human liver allografts.


METHODS
Immunohistochemistry and RT-PCR were performed in liver biopsies. To determine the effects of immunosuppression and cholestasis in IL-4 production, in vitro experiments were also designed.


RESULTS
IL-2 protein and its mRNA were absent in the liver, with minimal expression of IL-2 receptor, during rejection. In contrast, IL-4 protein and its mRNA were highly expressed during acute and chronic rejection, whereas this expression was absent in stable liver transplant recipients. In vitro, cyclosporine potently inhibited IL-2 and IL-2 receptor expression of activated mononuclear blood cells, but poorly inhibited IL-4 expression. Chenodeoxycholic acid decreased IL-2 and IL-2 receptor expression, but increased IL-4 expression.


CONCLUSIONS
During liver allograft rejection, IL-2 pathway is down-regulated, while IL-4 expression is increased by cholestasis and poorly inhibited by cyclosporine. These data suggest that IL-4 is involved in the mechanisms of liver allograft rejection in patients treated with cyclosporine.
Conti
F
F
Laboratoire d'Immunologie et de Biologie Cellulaire, Faculté de Médecine Cochin-Port-Royal, Université Paris V, France.
Calmus
Y
Y
Rouer
E
E
Gaulard
P
P
Louvel
A
A
Houssin
D
D
Zafrani
E S
ES
D000208:Acute Disease; D000328:Adult; D002779:Cholestasis; D002908:Chronic Disease; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000032:analysis / Q000235:genetics; D015847:Interleukin-4 / Q000032:analysis / Q000235:genetics*; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014184:Transplantation, Homologous
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D016572:Cyclosporine