scholarly journals Donor interleukin 1 receptor antagonist genotype associated with acute graft-versus-host disease in human leucocyte antigen-matched sibling allogeneic transplants

2001 ◽  
Vol 113 (3) ◽  
pp. 807-813 ◽  
Author(s):  
H. Cullup ◽  
A. M. Dickinson ◽  
G. H. Jackson ◽  
P. R. Taylor ◽  
J. Cavet ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Human Leucocyte Antigen ◽  
Interleukin 1 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 1 Receptor Antagonist ◽  
Matched Sibling ◽  
Acute Graft

Interleukin-1 blockade does not prevent acute graft-versus-host disease: results of a randomized, double-blind, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation

Blood ◽  
2002 ◽  
Vol 100 (10) ◽  
pp. 3479-3482 ◽  
Author(s):  
Joseph H. Antin ◽  
Daniel Weisdorf ◽  
Donna Neuberg ◽  
Roberta Nicklow ◽  
Shawn Clouthier ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Interleukin 1 ◽  
Double Blind ◽  
Host Disease ◽  
Double Blind Placebo ◽  
Graft Versus Host ◽  
Acute Graft

Acute graft-versus-host disease (GVHD) is thought to derive from direct T-cell injury of target tissues through perforin/granzyme, Fas/FasL interactions, and the effects of inflammatory cytokines. Animal models and some clinical trials support the notion that inhibition of inflammatory mediators such as interleukin-1 (IL-1), tumor necrosis factor α, and interferon γ may ameliorate or prevent GVHD. We hypothesized that blockade of IL-1 during the period of initial T-cell activation would reduce the risk of severe GVHD. We tested this hypothesis in a double-blind, placebo-controlled randomized trial of recombinant human IL-1 receptor antagonist (IL-1Ra) in 186 patients undergoing allogeneic stem cell transplantation. Randomization was stratified by degree of histocompatibility and stem cell source. All patients were conditioned with cyclophosphamide and total body irradiation. GVHD prevention consisted of cyclosporine and methotrexate in all patients. Recombinant human IL-1Ra or saline placebo was given from day −4 to day +10. Randomization was stratified according to GVHD risk. The 2 groups were well-matched for pretreatment characteristics. Moderate to severe GVHD (grades B-D) developed in 57 (61%) of 94 patients receiving IL-1Ra and in 51 (59%) of 86 patients on placebo (P = .88). There was no difference in hematologic recovery, transplantation-related toxicity, event-free survival, or overall survival. We conclude that blockade of IL-1 using IL-1Ra during conditioning and 10 days immediately after transplantation is not sufficient to reduce GVHD or toxicity or to improve survival.

Efficacy of the interleukin-2 receptor antagonist basiliximab in steroid-refractory acute graft-versus-host disease

2005 ◽  
Vol 130 (4) ◽  
pp. 568-574 ◽  
Author(s):  
Martin Schmidt-Hieber ◽  
Thomas Fietz ◽  
Wolfgang Knauf ◽  
Lutz Uharek ◽  
Werner Hopfenmuller ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Steroid Refractory ◽  
Acute Graft

scholarly journals Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease

Blood ◽  
1994 ◽  
Vol 84 (4) ◽  
pp. 1342-1348 ◽  
Author(s):  
JH Antin ◽  
HJ Weinstein ◽  
EC Guinan ◽  
P McCarthy ◽  
BE Bierer ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Response To Therapy ◽  
Mrna Levels ◽  
Steroid Resistant ◽  
Host Disease ◽  
Graft Versus Host

Abstract Acute graft-versus-host disease (GVHD) that is resistant to therapy is a highly lethal complication of marrow transplantation. Inflammatory cytokines such as interleukin-1 (IL-1) may be critical mediators of this process. If so, specific inhibition of IL-1 activity with recombinant human IL-1 receptor antagonist (IL-1Ra), a naturally occurring competitive inhibitor of IL-1, may ameliorate acute GVHD. We performed an open-label, phase I/II trial to evaluate the safety and efficacy of IL-1Ra in 17 patients with steroid-resistant GVHD. The IL- 1Ra was administered as a 24-hour continuous infusion over 7 days. The dose was escalated in cohorts of patients from 400 to 3,200 mg/d. Acute GVHD was evaluated in each affected organ and as an overall grade. Stage-specific improvement of acute GVHD occurred in the skin (8 of 14, 57%), gut (9 of 11, 82%), and liver (2 of 11, 18%). Overall, acute GVHD improved by at least one grade in 10 of 16 (63%) patients. Response to therapy was associated with a reduction of tumor necrosis factor-alpha (TNF-alpha) mRNA levels in blood mononuclear cells (P = .001). The only toxicity attributable to IL-1Ra was reversible transaminase elevation in two patients. Inhibition of IL-1 activity with IL-1Ra is safe and has demonstrable efficacy in acute GVHD that failed to respond to conventional treatment. These data provide further evidence that IL-1 is a mediator of GVHD.

scholarly journals Inhibition of interleukin-1 by an interleukin-1 receptor antagonist prevents graft-versus-host disease

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1915-1918 ◽  
Author(s):  
PL McCarthy ◽  
S Abhyankar ◽  
S Neben ◽  
G Newman ◽  
C Sieff ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Interleukin 1 ◽  
Allogeneic Bone Marrow Transplantation ◽  
Tnf Alpha ◽  
Allogeneic Bone ◽  
Necrosis Factor Alpha ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft-versus-host disease (GVHD) is the major complication of allogeneic bone marrow transplantation (BMT). Dysregulation of inflammatory monokines such as tumor necrosis factor alpha (TNF alpha) has been noted in both clinical and experimental GVHD. We present evidence that interleukin-1 (IL-1), another inflammatory monokine, is an important mediator of GVHD. Expression of the gene for IL-1 alpha as well as the gene for TNF alpha is increased in the skin of mice with GVHD. Inhibition of IL-1 function by the in vivo administration of IL-1 receptor antagonist (IL-1ra) reduces the immunosuppression and mortality of GVHD without impairing the engraftment of hematopoietic stem cells. GVHD thus appears to be a systemic inflammatory process in which monokines, especially IL-1, appear to be important mediators. Inhibition of IL-1 by IL-1ra represents a novel approach to the understanding and control of GVHD.

scholarly journals Therapy for severe refractory acute graft-versus-host disease with basiliximab, a selective interleukin-2 receptor antagonist

2006 ◽  
Vol 37 (10) ◽  
pp. 961-965 ◽  
Author(s):  
V A M Funke ◽  
C R de Medeiros ◽  
D C Setúbal ◽  
J Ruiz ◽  
M A Bitencourt ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Acute Graft

Donor clonal hematopoiesis increases risk of acute graft versus host disease after matched sibling transplantation

Leukemia ◽  
2021 ◽  
Author(s):  
Betül Oran ◽  
Richard E. Champlin ◽  
Feng Wang ◽  
Tomoyuki Tanaka ◽  
Rima M. Saliba ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Clonal Hematopoiesis ◽  
Matched Sibling ◽  
Acute Graft

scholarly journals Inhibition of interleukin-1 by an interleukin-1 receptor antagonist prevents graft-versus-host disease

Blood ◽  
1991 ◽  
Vol 78 (8) ◽  
pp. 1915-1918 ◽  
Author(s):  
PL McCarthy ◽  
S Abhyankar ◽  
S Neben ◽  
G Newman ◽  
C Sieff ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Interleukin 1 ◽  
Allogeneic Bone Marrow Transplantation ◽  
Tnf Alpha ◽  
Allogeneic Bone ◽  
Necrosis Factor Alpha ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Graft-versus-host disease (GVHD) is the major complication of allogeneic bone marrow transplantation (BMT). Dysregulation of inflammatory monokines such as tumor necrosis factor alpha (TNF alpha) has been noted in both clinical and experimental GVHD. We present evidence that interleukin-1 (IL-1), another inflammatory monokine, is an important mediator of GVHD. Expression of the gene for IL-1 alpha as well as the gene for TNF alpha is increased in the skin of mice with GVHD. Inhibition of IL-1 function by the in vivo administration of IL-1 receptor antagonist (IL-1ra) reduces the immunosuppression and mortality of GVHD without impairing the engraftment of hematopoietic stem cells. GVHD thus appears to be a systemic inflammatory process in which monokines, especially IL-1, appear to be important mediators. Inhibition of IL-1 by IL-1ra represents a novel approach to the understanding and control of GVHD.

Sign in / Sign up

Export Citation Format

Share Document