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 p atients with GVHD, and successful prevention and treatment of the dise ase with the use of cytokine antagonists to either the cytokine or its receptor, are only two of several factors demonstrating the involveme nt 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 pati ents 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 rec onstitution on cytokine serum levels was analyzed in detail in these c ohorts of patients by measuring interferon (IFN)-gamma, IFN-alpha, tum or necrosis factor-alpha, interleukin-6, neopterin, and beta 2-microgl obulin, The analyses showed that an increase in IFN-gamma and neopteri n serum levels was a specific feature of cyclophosphamide administrati on and was not observed after other cytostatic drugs or total body irr adiation, and that an increase in IFN-gamma, neopterin, beta 2-microgl obulin, and IFN-alpha release depends on the presence of T cells in th e graft. We conclude that significant cytokine serum alterations were noted after TCD BMT as compared with after non-TCD BMT. These alterati ons, besides depletion of cytotoxic effector cells, might be involved in preventing GVHD after TCD BMT, In addition, more attention should b e devoted to the cytokine release-inducing capacity of the conditionin g regimen, because such a release might influence the occurrence of tr ansplant related complications after BMT.