Association of serum interleukin-7 levels with the development of acute graft-versus-host disease.
OBJECTIVE
Morbidity from acute graft-versus-host disease (GVHD) limits the success of allogeneic hematopoietic stem-cell transplantation (HSCT) to treat malignancy. Interleukin-7 (IL-7), the principal homeostatic cytokine for T cells, is required for acute GVHD in murine models. In contrast to inflammatory cytokines (eg, IL-2, tumor necrosis factor alpha), IL-7 has not been studied extensively in the clinical transplant setting relative to its relationship with acute GVHD.


METHODS
We evaluated the association of serum IL-7 levels with acute GVHD in 31 patients who were uniformly treated in a prospective clinical trial with reduced-intensity allogeneic HSCT from human leukocyte antigen-identical siblings. GVHD prophylaxis consisted of cyclosporine and methotrexate. Serum IL-7 levels and lymphocyte populations were determined at enrollment, the day of transplantation before the allograft infusion, and at specified intervals through 12 months post-transplantation.


RESULTS
As expected, IL-7 levels were inversely correlated with T-cell populations (P < .00001). Acute GVHD was significantly associated with higher IL-7 levels at day +7 (P = .01) and day +14 (P = .00003) post-transplantation as well as with the allograft CD34(+) cell dose (P = .01). IL-7 levels at day +14 also correlated with the severity of acute GVHD (P < .0001). In logistic regression models, these factors were highly sensitive (up to 86%) and specific (100%) for classifying whether patients developed acute GVHD.


CONCLUSIONS
These data support preclinical observations that IL-7 plays a critical role in inducing acute GVHD and provide a rational basis for novel approaches to prevent and treat acute GVHD through modulation of the IL-7 pathway.
Dean
Robert M
RM
Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Fry
Terry
T
Mackall
Crystal
C
Steinberg
Seth M
SM
Hakim
Fran
F
Fowler
Daniel
D
Odom
Jeanne
J
Foley
Jason
J
Gress
Ronald
R
Bishop
Michael R
MR
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D017252:CD3 Complex / Q000032:analysis; D018791:CD4 Lymphocyte Count; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000517:prevention & control; D006680:HLA Antigens / Q000032:analysis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015851:Interleukin-7 / Q000097:blood*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D035781:Siblings; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D015415:Biomarkers; D017252:CD3 Complex; D016827:CD8 Antigens; D006680:HLA Antigens; C508605:IL7 protein, human; D007166:Immunosuppressive Agents; D015851:Interleukin-7