Tehran University Medical Journal

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Background: Graft-versus-host disease is one of the major complications after allogenic bone marrow transplantation, but it is not easy to anticipate the onset. Cytokines released by type 1 T-helper cells are thought to play a pivotal role in acute graft-versus-host disease (aGVHD). The ability to predict the likely occurrence of graft-versus-host-disease (GVHD) after BMT would be extremely valuable. By serially measuring serum levels of soluble IL-2 receptor (sIL-2R), IL-18 and following allogeneic bone marrow transplantation (BMT), we tried to define their relationship to aGVHD as complication of the transplantation and determine useful markers for aGVHD predictors.

Materials and Methods: Serum sIL-2R, IL-18, and levels were measured by sandwich ELISA in 219 sera samples from 39 patients (with hematological disorders before and after allogeneic BMT) and 28 controls. All patients received BMT from HLA-identical siblings.

Results: 25 patients developed aGVHD and serum levels of sIL-2 R and IL-18 , in sera drawn before transplantation , in patients with acute graft-versus-host disease (aGVHD +) , were increased in comparison of patients without acute graft-versus-host disease (aGVHD ¯) and control group and there wasn’t any significant differences in serum levels of sIL-2 R and IL-18 in aGVHD ¯ patients and controls. Serum level of IL-18, in aGVHD+ patients, was increased during day 3 - 24 after BMT, and there was a significant difference in patients with GVHD 0 – GVHD III. In majority of patients with acute GVHD (60 %) , the peak levels of IL-18 and IL-2R was achieved on day 10 after BMT and the rise in sIL-2R and IL-18 preceded of clinical signs of GVHD (mean day 15 after BMT). Level of IL-18 in patients with aGVHD had strongly correlated with the severity of aGVHD on Day 10 after BMT. IL-18 level mean (before BMT), in patients who received Busulfan and Fludarabin to treat aGVHD, was lower than in patients who received Busulfan - Endoxan, or Cyclophosphamide.

Conclusion: Our data concluded that IL-18 plays an important role in the development of aGVHD and IL-18 level might be an indicator for aGVHD, reflecting the severity of the disease. These findings suggest that IL-18 may play important roles in the pathogenesis of aGVHD and that measurement of serum IL-18 levels can be useful predictor of aGVHD.

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Background: Tumor necrosis factor alpha (TNF-) is a major mediator of inflammatory responses and also plays a role in Febrile non-hemolytic reactions (FNHRs) after platelet concentrates (PCs) injection. It is thought contaminating WBCs are the source of these cytokine so inactivating or decreasing of these WBCs will be effective to decline of the cytokines. Due to difference results between different methods for TNF measurement, in this study we compared Immunoassay and Bioassay methods to determine TNF- in supernatants of PCs.
Materials and Methods: TNF- was measured by ELISA (Immunoassay) and by the L929 cytotoxicity Bioassay in supernatant of random donor PCs (RD-PC) prepared by platelet rich plasma (PRP). These platelet concentrates were divided in 4 groups: 1- unfiltered , non-irradiated RD-PCs (N=13) 2- unfiltered and -irradiated RD-PCs (N=16) 3- filtered , non-irradiated RD-PCs (N=14) 4- filtered and -irradiated RD-PCs (N=11)
Results: Our results showed: • TNF-  was increased (by ELISA) in unfiltered non-irradiated units during storage but not in -irradiated and filtered RD-PCs in day 3. Compared to unfiltered PCs in filtered units, pre-storage filtration and irradiation prevented a rise in the TNF-  in day 3 of storage. • There was no correlation between ELISA and the cytotoxicity L929 bioassay .
Conclusion: It has been previously reported that different quantitative results can be obtained when TNF alpha is measured in biological fluids by Bioassay and Immunoassay. This is thought to be related to the presence of antigenic forms of TNF alpha that cannot be detected by bioassay, such as complexes with soluble receptors (sTNF-R) or TNF alpha monomers.