Serum cytokine levels after HLA-identical bone marrow transplantation.
BACKGROUND
Altered profiles of cytokine production are observed after bone marrow transplantation (BMT). The presence of certain cytokines in serum can be indicative for BMT-related complications, such as graft-versus-host disease (GVHD) and infections. The putative correlation between abnormal serum cytokine levels and BMT-related complications was further analyzed in this retrospective study.


METHODS
Serum levels of a panel of cytokines and cytokine-associated molecules (i.e., interleukin [IL]-1alpha, IL-1beta, IL-4, IL-6, IL-10, IL-12, IL-1 receptor antagonist, and the soluble a chain of the IL-2 receptor [sIL-2R alpha]) were assessed in 329 sera of 46 patients who had undergone HLA-identical or autologous BMT. Serum cytokine levels of the BMT donor and of the patients before BMT and at different time points during the post-BMT period were measured. The results were correlated with relapse, acute GVHD, chronic GVHD, and infections.


RESULTS
Serum levels of IL-1alpha, IL-1beta, IL-4, and IL-12 were undetectable. The transplantation regimen itself causes a significant rise in IL-10 and sIL-2R alpha levels in patients receiving allogeneic bone marrow. In the post-BMT period, increased IL-6 serum levels were significantly correlated with infections. Increased IL-10 levels were significantly correlated with acute graft-versus-host disease, chronic GVHD, and infections. Increased sIL-2R alpha levels were correlated with chronic GVHD, as were IL-1 receptor antagonist levels.


CONCLUSIONS
During the post-HLA-identical BMT period, the serum cytokine levels of IL-6 were enhanced during infections, whereas the sIL-2R alpha levels were increased during chronic GVHD. The serum levels of IL-10 and of the cytokine-related molecule IL-1ra were enhanced during both infections and chronic GVHD. These results further substantiate the complex cytokine cascade that is initiated by the conditioning regimen and that evolves further in reaction to BMT-related complications and their treatments.
Liem
L M
LM
Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands.
van Houwelingen
H C
HC
Goulmy
E
E
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000097:blood*; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood; D006680:HLA Antigens / Q000145:classification*; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D018664:Interleukin-12 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D015375:Receptors, Interleukin-2 / Q000097:blood; D012016:Reference Values; D012189:Retrospective Studies; D012795:Sialoglycoproteins / Q000097:blood; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D016207:Cytokines; D006680:HLA Antigens; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D012795:Sialoglycoproteins; D018664:Interleukin-12