Higher Interleukin-10 (IL-10) and Lower Interferon-Gamma (IFN-γ), Tumor Necrosis Factor Alpha (TNF-α), IL-6, IL-8 Serum Levels in Patients Undergoing Reduced Intensity Versus Conventional Intensity Conditioning Hematopoietic Cell Transplantation (HCT).

Endogenous cytokines play an essential role in allogeneic HCT not only for hematopoietic reconstitution but also for the most frequent complications of HCT such as graft-versus-host disease (GvHD). Cytokines have important immune modulatory effects and are therefore important determinants for outcome. No report, however, exists to date on the role of cytokines in HCT with reduced intensity conditioning (RIC), which are associated with less severe GVHD and reduced transplant related mortality. Patients transplanted at the University of Leipzig between October 2000 and November 2001 with an autologous (n=10) or allogeneic (n=38) related or unrelated graft were included in this analysis. The median age of patients was 49 (range 21–69) years. Preparative regimens for the allogeneic HCT consisted of conventional (n=20) or RIC (n=18) conditioning.

Cyclophosphamide (60mg/kg for 2 consecutive days) was given either with busulfan (4 mg/kg per day for 4 days; n=9) or fractioned total body irradiation (TBI 12 Gy; n=11) for conventional HCT and cyclosporine in combination with metotrexate was used as GvHD prophylaxis. In contrast, patients with the reduced intensity treatment received low dose TBI (2 Gy) in combination with fludarabine (30 mg/m² per day for 3 consecutive days) followed by cyclosporine and mycophenolat mofetil. Serum was collected three times weekly and was frozen at −70° until measurement. Cytokine-serum-levels were analyzed with a Multiplex Cytokine Assay (Bio-Plex, Bio-Rad Laboratories, Hercules, CA).

Endogenous IFN-γ and TNF-α showed similar fluctuations after RIC and non-RIC HCT with peak levels between day 14/17. However, serum levels of non-RIC patients increased faster than serum levels of RIC-patients. Higher IL-4 serum levels were detected in the RIC patients as compared to the non-RIC patients especially in the later course of HCT. In contrast, higher IL-6 and IL-8 values with peaks at d 6/9 in both groups were observed in the patients with conventional HCT. Similarly a difference for IL-13 levels was detected with higher values for the conventional group. The most prominent difference was observed in the endogenous IL-10 production with significant higher IL-10 levels in RIC compared to non-RIC patients.

We concluded that serum levels of IL-4 and IL-10 were higher and IFN-γ, TNF-α, IL-6, IL-8 and IL-13 lower in the RIC compared to the non-RIC group. These results are in line with previous work on cytokines after conventional preparative regimen and might provide an explanation for the lower transplant related mortality of RIC regimens.