Abstract (EN):
Rapamycin (RAPA) is a new immunosuppressive drug that operates distally to cytokine ligation to their receptors. Previously, we have shown that RAPA induces significant changes on renal transplants (RTX) aspiration biopsy sample cultures synthesis of IL-1ra, IL-2, IL-6, IL-10, MCP-1, TGF-ß1 and soluble (s)TNFRI. Furthermore, we have observed that IL-2, IL-6, sTNFRI, sTNFRII, sIL-2-receptor-¿, produced by aspiration biopsy cultures are significantly correlated with acute rejection in RTX. Cytokines present in blood circulation are not helpful for the diagnosis of immunologic events post-RTX but some of their receptors, which are much more stable than cytokines might assist on immunologic surveillance post-RTX. We hypothesized that some cytokine receptors present in circulation might be modulated by rapamycin. Twelve cadaver RTX treated with RAPA were compared to eighteen cadaver RTX treated with MMF. Both groups also received CsA and prednisolone.All RTX remained rejection-free for the first six months at least. Both were studied on day seven post-RTX. sIL-lRII, sIL-2- receptor-¿, sIL-6R, sTNFRI and sTNFRII were measured by ELISA, R&D, USA. We did not find any significant differences comparing both groups for HLA matching, PRA before RTX, serum creatinine on day seven and blood CsA levels. The values are expressed in pg/ml, RAPA /MMF order. SIL-lRII: 31285±9313/26704±7833; sIL-2-receptor-¿: 5096±2537/2954±1170; sIL-6R: 54233±13414/45591±10189; sTNFRI: 8861±4593/4610±2508; sTNFRII: 9338±3166/6626±2214. All are significantly different, P=0.012, 0.011, 0.011,0.0007 and 0.019, respectively (Kruskal-Wallis). We conclude that RAPA down-regulates serum cytokine receptors compared to MMF in the early days of RTX. As three of the cytokine receptors studied have been shown to be associated with acute rejection when they are evaluated on aspiration biopsy culture supematants, our data would suggest these RAPA induced changes may be associated with a stronger immunosuppression. © 2001 Blackwell Science Ltd.
Language:
English
Type (Professor's evaluation):
Scientific