Interleukin 7 worsens graft-versus-host disease

被引:91
作者
Sinha, ML
Fry, TJ
Fowler, DH
Miller, G
Mackall, CL
机构
[1] NCI, Pediat Oncol Branch, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA
[2] NIH, Vet Resources Program, Bethesda, MD 20892 USA
关键词
D O I
10.1182/blood-2002-04-1082
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Impaired immune reconstitution has moved to the forefront of clinical problems limiting progress In allogeneic bone marrow transplantation (BMT). The Identification of therapies that can enhance immune reconstitution by increasing thymopoiesis is critical to solving this problem. Interleukin 7 (IL-7) is the most potent thymopoietic cytokine identified thus far. To study the effects of IL-7 on immune reconstitution and graft-versus-host disease (GVHD) following allogeneic BMT, we administered recombinant human IL-7 (rhIL-7) in a murine parent into an F1 model. Results showed that rhIL-7 therapy lowered the "threshold" T-cell dose required to induce both clinical signs of GVHD as well as lethal GVHD. Histologic analysis of GVHD target tissues revealed that rhIL-7 Increased the degree of Inflammation and tissue damage observed at all T-cell doses studied, but did not change the pattern of organs affected or the histologic appearance of the GVHD within target organs. In addition, we evaluated the capacity for rhIL-7 to enhance thymopoiesis In the setting of allogeneic T cell-depleted (TCD) and T-cell-replete BMT. We observed that rhIL-7 therapy enhanced thymic function In TCD allogeneic BM transplant recipients, but not In animals that received even modest doses of T cells presumably due to thymic toxicity of the graft-versus-host reaction. Thus, caution must be exercised as IL-7 is developed clinically as an immunorestorative agent for use In the setting of allogeneic BMT. These results suggest that use of IL-7 should be limited to the setting of TCD BMT to obtain the greatest benefit on Immune competence with the least toxicity. (C) 2002 by The American Society of Hematology.
引用
收藏
页码:2642 / 2649
页数:8
相关论文
共 61 条
[1]   Interleukin-7-enhanced cytotoxic T lymphocyte activity after viral infection in marrow transplanted mice [J].
AbdulHai, A ;
BenYehuda, A ;
Weiss, L ;
Friedman, G ;
ZakayRones, Z ;
Slavin, S ;
Or, R .
BONE MARROW TRANSPLANTATION, 1997, 19 (06) :539-543
[2]   Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease [J].
Alpdogan, O ;
Schmaltz, C ;
Muriglan, SJ ;
Kappel, BJ ;
Perales, MA ;
Rotolo, JA ;
Halm, JA ;
Rich, BE ;
van den Brink, MRM .
BLOOD, 2001, 98 (07) :2256-2265
[3]   IL-7 and not stem cell Factor Reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice [J].
Andrew, D ;
Aspinall, R .
JOURNAL OF IMMUNOLOGY, 2001, 166 (03) :1524-1530
[4]  
ARMITAGE RJ, 1991, ADV EXP MED BIOL, V292, P121
[5]   Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype [J].
Aversa, F ;
Tabilio, A ;
Velardi, A ;
Cunningham, I ;
Terenzi, A ;
Falzetti, F ;
Ruggeri, L ;
Barbabietola, G ;
Aristei, C ;
Latini, P ;
Reisner, Y ;
Martelli, MF .
NEW ENGLAND JOURNAL OF MEDICINE, 1998, 339 (17) :1186-1193
[6]  
BESCHORNER WE, 1978, AM J PATHOL, V92, P173
[7]   RECOMBINANT HUMAN IL-7 ADMINISTRATION IN MICE AFFECTS COLONY-FORMING UNITS-SPLEEN AND LYMPHOID PRECURSOR CELL LOCALIZATION AND ACCELERATES ENGRAFTMENT OF BONE-MARROW TRANSPLANTS [J].
BOERMAN, OC ;
GREGORIO, TA ;
GRZEGORZEWSKI, KJ ;
FALTYNEK, CR ;
KENNY, JJ ;
WILTROUT, RH ;
KOMSCHLIES, KL .
JOURNAL OF LEUKOCYTE BIOLOGY, 1995, 58 (02) :151-158
[8]   GROWTH-FACTORS CAN ENHANCE LYMPHOCYTE SURVIVAL WITHOUT COMMITTING THE CELL TO UNDERGO CELL-DIVISION [J].
BOISE, LH ;
MINN, AJ ;
JUNE, CH ;
LINDSTEN, T ;
THOMPSON, CB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (12) :5491-5495
[9]  
Bolotin E, 1996, BLOOD, V88, P1887
[10]   Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count [J].
Bolotin, E ;
Annett, G ;
Parkman, R ;
Weinberg, K .
BONE MARROW TRANSPLANTATION, 1999, 23 (08) :783-788