In vivo IL-10 and TGF-beta production by PBMC from long-term kidney transplant recipients with excellent graft function: a possible feedback mechanism participating in immunological stability.
BACKGROUND
Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) are Th2-derived multifunctional cytokines that exhibit potent immunoregulatory and anti-inflammatory properties which might prolong graft survival. The aim of this study was to explore whether spontaneous production of IL-10 and TGF-beta by blood mononuclear cells correlates with excellent long-term graft function.


METHODS
A cross-sectional study was carried out in 32 kidney transplant recipients, without albuminuria, treated with azathioprine and prednisone. Spontaneous IL-10 and TGF-beta were measured by enzyme-linked immunosorbent assay in supernatants from 24 h cultured unstimulated peripheral blood mononuclear cells. Both cytokines were also determined in 10 healthy kidney donors.


RESULTS
There was no correlation between IL-10 or TGF-beta with any variable tested, namely age, SCr, histocompatibility, and post-transplant follow-up. In vivo IL-10 production displayed a statistical trend to be higher in transplant recipients than in controls (362.3 +/- 465, range 12.5-1929.3 pg/ml, and 189 +/- 170, range 4.17-485.7 pg/ml, respectively; p = 0.08), whereas no difference was observed in TGF-beta among the same groups (134.7 +/- 79.2, range 68-421 pg/ml, and 121.4 +/- 25.8, range 75-151 pg/ml, respectively). Interestingly, a statistically significant inverse correlation was observed between IL-10 and TGF-beta in kidney transplant recipients (p = 0.03).


CONCLUSIONS
The higher IL-10 production observed in long-term kidney transplant recipients supports the notion that this cytokine contributes in decreasing allogenic immune responses and allows prolongation of allograft survival. The balance between TGF-beta and IL-10 may be of paramount importance in graft acceptance.
Alberú
Josefina
J
Transplantation, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico. josefinanlberu@hotmail.com.or
Richaud-Patin
Yvonne
Y
Vázquez-Lavista
Luis Gabriel
LG
de Leo
Claudia
C
Guzmán-Rodríguez
Hugo
H
Mancilla
Eduardo
E
Correa-Rotter
Ricardo
R
Chew-Wong
Alfredo
A
Llorente
Luis
L
D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000627:therapeutic use; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016753:Interleukin-10 / Q000096:biosynthesis*; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D001379:Azathioprine; D011241:Prednisone