Interleukin-15 production during liver allograft rejection in humans.
BACKGROUND
The activity of interleukin (IL)-15, a cytokine produced by macrophages, is similar to that of IL-2. We investigated whether IL-15 plays a role in liver allograft rejection.


METHODS
We evaluated plasma levels and intrahepatic expression of IL-15 in 35 patients after liver transplantation, and then analyzed in vitro the influence of anticalcineurin drugs or steroids on IL-15 production and secretion. Finally, we examined the effects of IL-15 on lymphocyte proliferation in mixed lymphocyte culture in the presence or absence of anticalcineurin drugs or steroids.


RESULTS
Plasma levels and in situ expression of IL-15 were enhanced during liver allograft rejection, particularly during steroid-resistant acute rejection and during chronic rejection. In vitro, IL-15 production and secretion were inhibited by neither anticalcineurin drugs nor steroids. Exogenous IL-15 enhanced cell-mediated immune response, and this effect was not inhibited by immunosuppressive drugs.


CONCLUSIONS
IL-15 can play a role in the initiation and outcome of acute and chronic rejection. Anti-IL-15 therapy in combination with classic immunosuppression therapy might thus be beneficial in the prevention of acute, and especially chronic, allograft rejection.
Conti
Filomena
F
Laboratoire de Biologie Cellulaire, Faculté de Médecine Cochin-Port-Royal, Paris, France.
Frappier
Jerome
J
Dharancy
Sebastien
S
Chereau
Christiane
C
Houssin
Didier
D
Weill
Bernard
B
Calmus
Yvon
Y
D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D019409:Interleukin-15 / Q000097:blood / Q000235:genetics*; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000276:immunology
D015415:Biomarkers; D019409:Interleukin-15