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

Joseph H. Antin, Howard J. Weinstein, Eva C. Guinan, Philip McCarthy, Barbara E. Bierer, D. Gary Gilliland, Susan K. Parsons, Karen K. Ballen, Llonna J. Rimm, Giorgio Falzarano, Duane C. Bloedow, Lori Abate, Mel Lebsack, Steven J. Burakoff, James L.M. Ferrara

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133 Scopus citations


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-α (TNF-α) 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.

Original languageEnglish
Pages (from-to)1342-1348
Number of pages7
Issue number4
StatePublished - 15 Aug 1994


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