The study of bone mesenchymal stem cells combined with interleukin-6 monoclonal antibody induce immune tolerance of rat heart transplantation

Objective To search for the effect and mechanism of immune tolerance that bone mesenchymal stem cells (MSCs) and Interleukin-6 monoclonal antibody (IL-6 mAb) affect rat heart transplantation. Methods Donor (SD rats) and receptor (Wistar rats) of 20 were randomly divided into four groups, GroupⅠ: The heart from SD rat was transplanted into the abdomen of Wistar rat. GroupⅡ: receptors of Wistar rats were injected normal saline daily 0.2 ml before surgery for five consecutive days and after heart transplantation for 3 days via jugular vein. Group Ⅲ: receptor was injected mesenchymal stem cells 1×106/0.2 ml before surgery for five consecutive days and after heart transplantation for 3 days via jugular vein. Group Ⅳ: receptor Wistar rat were injected MSCs and IL-6 mAb [100 μg/(kg·d)] before surgery for five consecutive days and after heart transplantation for 3 days via jugular vein. Testing Items: cardiac allograft survival time, donor heart pathological changes, receptor of CD4+ CD25+ regulatory T (Treg)cell change, T helper cell 17 (Th17) ’ s change, the expression of forkhead box P3 (FoxP3) protein in the Treg cells and serum transforming growth factor-beta1 (TGF-β1), Interleukin-10 (IL-10), Interleukin-2 (IL-2), Interleukin-6 (IL-6), Interleukin-17 (IL-17) change. Results The average survival time of group Ⅳ [(40.800±8.815) d] was longer than other groups [Ⅰ: (7.600±1.140) d; Ⅱ: (8.600±1.817) d; Ⅲ: (21.800±1.304) d]; The peripheral blood CD4+ CD25+ Treg [Ⅰ: (4.70±0.15)%; Ⅱ: (4.90±0.40)%; Ⅲ: (11.22±0.28)%; Ⅳ: (21.40±0.62))%], FoxP3 protein expression rate [Ⅰ: (71.21±1.05)%; Ⅱ: (71.07±1.41)%; Ⅲ: (72.69±3.84)%; Ⅳ: (96.24±1.42)%], TGF-β1 [Ⅰ: (165.52±8.68) pg/ml; Ⅱ: (169.73±3.45) pg/ml; Ⅲ: (339.38±13.40) pg/ml; Ⅳ: (475.79±10.11) pg/ml], IL-10 [Ⅰ: (29.03±1.05) pg/ml; Ⅱ: (30.40±1.63) pg/ml; Ⅲ: (88.65±1.84) pg/ml; Ⅳ: (136.14±2.32) pg/ml] of Group Ⅲ and group Ⅳwere significantly higher than groupⅠand group Ⅱ and Group Ⅳ was higher than group Ⅲ; The peripheral blood th17 cell ratio [Ⅰ: (7.18±0.48)%; Ⅱ: (6.98±0.61)%; Ⅲ: (4.16±0.23)%; Ⅳ: (1.28±0.19)%], IL-2 [Ⅰ: (112.94±3.52) pg/ml; Ⅱ: (111.48±2.71) pg/ml; Ⅲ: (66.96±1.04) pg/ml; Ⅳ: (33.31±1.41) pg/ml], IL-6 [Ⅰ: (70.96±1.20) pg/ml; Ⅱ: (70.06±2.10) pg/ml; Ⅲ: (42.94±2.14) pg/ml; Ⅳ: (16.57±1.05) pg/ml], IL-17 [Ⅰ: (96.86±1.15) pg/ml; Ⅱ: (92.72±4.91) pg/ml; Ⅲ: (49.49±1.63) pg/ml; Ⅳ: (21.22±0.82) pg/ml] of Group Ⅲ and group Ⅳwere significantly lower than groupⅠand group Ⅱ and group IV is lower than group Ⅲ. Conclusion Bone mesenchymal stem cells and IL-6 mAb can significantly increase the receptors’ proportion of CD4+ CD25+ FoxP3+ Treg cells, reduce the proportion of Th17 cells, lower down IL-2, IL-17, IL-10, increase the expression of of TGF-β1 immune factors. So they can significantly extend the survival time of rats heart of transplantation. Key words: Mesenchymal stem cells; Interleukin-6 monoclonal antibody; Cardiac transplantation; Immunotolerance