PMID- 11923692
OWN - NLM
STAT- MEDLINE
DCOM- 20020422
LR  - 20220321
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 73
IP  - 6
DP  - 2002 Mar 27
TI  - Compared to mycophenolate mofetil, rapamycin induces significant changes on 
      growth factors and growth factor receptors in the early days post-kidney 
      transplantation.
PG  - 915-20
AB  - BACKGROUND: The new immunosuppressive drug Rapamycin (Rapa) is endowed with a 
      mechanism of action that is distinct from that of calcineurin inhibitors. It has 
      been claimed that Rapa does not significantly modulate either the cytokine 
      expression or the transcription of several growth factors in mitogen-activated T 
      cells. Previously, we reported that fine-needle aspiration biopsy (FNAB) sample 
      cultures synthesize a large array of cytokines, and some of them may be powerful 
      predictors of acute rejection in renal transplants. We hypothesized that Rapa may 
      induce significant changes on cytokine production by FNAB sample cultures and on 
      serum cytokine receptors when compared to other immunosuppressive drugs. METHODS: 
      Kidney transplants treated with CsA-Rapa-Pred (Rapa group) were compared with 
      transplants treated with CsA-mycophenolate mofetil-Pred (MMF group). They were 
      studied on day 7 posttransplantation, and they remained rejection free for at 
      least the first 6 months. FNAB samples were cultured and the supernatants were 
      collected at 48 hr of incubation and analyzed by ELISA for interleukin 1 receptor 
      antagonist (IL-1ra), IL-2, IL-6, IL-10, IL-18, monocyte chemotactic protein 1 
      (MCP-1), soluble tumor necrosis factor I, and transforming growth factor 
      (TGF)-beta(1). The soluble receptors for IL-1, IL-2, IL-6, and tumor necrosis 
      factor alpha, together with IL-2 and IL-18 were also measured in serum. RESULTS: 
      Significant differences were observed when comparing Rapa with the MMF group. 
      IL-18 and TGF-beta(1) synthesis were up-regulated, whereas IL-6 and MCP-1 were 
      down-regulated in FNAB sample cultures. The Rapa group showed a significant 
      down-regulation of each cytokine receptor and of IL-2 in serum. CONCLUSIONS: Rapa 
      was associated with a decreased synthesis of primarily monocyte-derived cytokines 
      and enhanced production of TGF-beta(1), which in an appropriate cytokine milieu 
      may promote allograft tolerance. The down-regulation of cytokine receptors and 
      IL-2 may be associated with a depressed immune response towards the kidney 
      allograft.
FAU - Oliveira, Jose G G
AU  - Oliveira JG
AD  - Renal Department, Hospital S. Joao, Porto, Portugal.
FAU - Xavier, Paula
AU  - Xavier P
FAU - Sampaio, Susana M
AU  - Sampaio SM
FAU - Henriques, Castro
AU  - Henriques C
FAU - Tavares, Isabel
AU  - Tavares I
FAU - Mendes, Armando A
AU  - Mendes AA
FAU - Pestana, Manuel
AU  - Pestana M
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Cytokines)
RN  - 0 (Growth Substances)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Receptors, Growth Factor)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - HU9DX48N0T (Mycophenolic Acid)
RN  - VB0R961HZT (Prednisone)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Biopsy, Needle
MH  - Cyclosporine/therapeutic use
MH  - Cytokines/biosynthesis
MH  - Drug Therapy, Combination
MH  - Graft Rejection/*prevention & control
MH  - Growth Substances/*metabolism
MH  - Histocompatibility Testing
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Kidney Transplantation/immunology/pathology/*physiology
MH  - Middle Aged
MH  - Monocytes/immunology
MH  - Mycophenolic Acid/*analogs & derivatives/*therapeutic use
MH  - Postoperative Period
MH  - Prednisone/therapeutic use
MH  - Receptors, Growth Factor/*metabolism
MH  - Sirolimus/*therapeutic use
EDAT- 2002/03/30 10:00
MHDA- 2002/04/23 10:01
CRDT- 2002/03/30 10:00
PHST- 2002/03/30 10:00 [pubmed]
PHST- 2002/04/23 10:01 [medline]
PHST- 2002/03/30 10:00 [entrez]
AID - 10.1097/00007890-200203270-00015 [doi]
PST - ppublish
SO  - Transplantation. 2002 Mar 27;73(6):915-20. doi: 10.1097/00007890-200203270-00015.