Serum levels of cytokines and secondary messages after T-cell-depleted and non-T-cell-depleted bone marrow transplantation: influence of conditioning and hematopoietic reconstitution.
Cytokines are increasingly recognized as important mediators of graft-versus-host disease (GVHD). Measurements of cytokine serum levels in patients with GVHD, and successful prevention and treatment of the disease with the use of cytokine antagonists to either the cytokine or its receptor, are only two of several factors demonstrating the involvement of cytokines in GVHD. To further investigate the role of cytokines in the pathomechanism of acute GVHD, we investigated endogenous serum levels of various cytokines and dependent molecules in sera of 14 patients after T-cell-depleted (TCD) bone marrow transplantation (BMT) and compared the results with those of 12 patients undergoing non-TCD BMT. The effect of various conditioning regimens and of hematopoietic reconstitution on cytokine serum levels was analyzed in detail in these cohorts of patients by measuring interferon (IFN)-gamma, IFN-alpha, tumor necrosis factor-alpha, interleukin-6, neopterin, and beta2-microglobulin. The analyses showed that an increase in IFN-gamma and neopterin serum levels was a specific feature of cyclophosphamide administration and was not observed after other cytostatic drugs or total body irradiation, and that an increase in IFN-gamma, neopterin, beta2-microglobulin, and IFN-alpha release depends on the presence of T cells in the graft. We conclude that significant cytokine serum alterations were noted after TCD BMT as compared with after non-TCD BMT. These alterations, besides depletion of cytotoxic effector cells, might be involved in preventing GVHD after TCD BMT. In addition, more attention should be devoted to the cytokine release-inducing capacity of the conditioning regimen, because such a release might influence the occurrence of transplant-related complications after BMT.
Schwaighofer
H
H
Department of Internal Medicine, Innsbruck University Hospital, Austria.
Kernan
N A
NA
O'Reilly
R J
RJ
Brankova
J
J
Nachbaur
D
D
Herold
M
M
Eibl
B
B
Niederwieser
D
D
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D001854:Bone Marrow Cells; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D008212:Lymphocyte Depletion; D051379:Mice; D019798:Neopterin; D011817:Rabbits; D015290:Second Messenger Systems / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D016207:Cytokines; D001708:Biopterins; D019798:Neopterin