Treatment with granulocyte colony-stimulating factor increases interleukin-1 receptor antagonist levels during engraftment following allogeneic stem-cell transplantation.
BACKGROUND
The effect of treatment with granulocyte colony-stimulating factor (G-CSF) on interleukin-1 receptor antagonist (IL-1ra) plasma concentrations as well as the role of IL-1ra on leucocyte recovery and parameters of infection within the first 30 days after haematopietic stem-cell transplantation (HSCT) are not well known.


METHODS
Twenty-seven patients undergoing myeloablative therapy followed by allogeneic SCT for various haematological disorders were either treated with (n = 18) or without (n = 9) G-CSF. IL-1ra plasma levels were serially determined by ELISA starting at day - 1 and continued until patients were engrafted.


RESULTS
Patients receiving G-CSF had significantly shorter neutropenic periods and significantly lower mean C-reactive protein serum levels during the first 3 weeks succeeding bone marrow transplantation (BMT). Importantly, starting at day + 11 and paralleling the rise of peripheral blood leucocytes, increasing IL-1ra plasma concentrations were observed in both treatment groups. However, the magnitude of the IL-1ra surge was far greater in the G-CSF treatment group. Peak IL-1ra plasma level observed on day + 19 was 882.3 +/- 879.2 pg mL(-1) (mean +/- SD) in patients receiving G-CSF compared with 285.8 +/- 175.2 pg mL(-1) (mean +/- SD) in patients not receiving G-CSF (P = 0.0130). Furthermore, a direct correlation of IL-1ra with peripheral blood leucocytes was verified by the Spearman rank test (P = 0.0025).


CONCLUSIONS
Granulocyte colony-stimulating factor-mediated acceleration of neutrophil recovery following myeloablative therapy correlated with increased IL-1ra plasma concentrations. Our data suggest that IL-1ra constitutes an intrinsic component of the anti-inflammatory and neutrophil differentiating efficacy of G-CSF and, thus, IL-1ra may be required for the in vivo activity of G-CSF.
Schwabe
M
M
Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany.
Hartert
A-M
AM
Bertz
H
H
Finke
J
J
D016026:Bone Marrow Transplantation / Q000379:methods*; D002097:C-Reactive Protein / Q000032:analysis; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000601:surgery; D007958:Leukocyte Count; D009503:Neutropenia / Q000188:drug therapy; D011184:Postoperative Period; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*
D017472:Receptors, Interleukin-1; D016179:Granulocyte Colony-Stimulating Factor; D002097:C-Reactive Protein