Anti-thymocyte globulin in haematology: Recent developments

Anti-thymocyte globulin (ATG) is a polyclonal antiserum introduced into clinical medicine more than 30 years ago. It induces a broad non-specific immunosuppression. In haematology, standard indications are severe aplastic anaemia and prophylaxis and treatment of graft-versus-host disease (GVHD) (after allogeneic transplantation). For aplastic anaemia, ATG from horses has been found to be superior to ATG from rabbits. In the situation of allogeneic transplantation, ATG lessens the risk of chronic GVHD but may not improve survival. There is current controversy regarding which patients benefit most from ATG and what the ideal dosage is. It is likely that in the coming years a more specific immunosuppressive will be developed that will minimize GVHD while maintaining the graft-versus-malignancy effect.

Immunosuppressive Effect of Exosomes from Mesenchymal Stromal Cells in Defined Medium on Experimental Colitis

BACKGROUND AND OBJECTIVES: The exosomes released by mesenchymal stromal cells (MSCs) in classical FBS-containing media have been demonstrated as an alternative, cell-free therapy in various diseases including inflammatory bowel disease (IBD). It has been found that the function of exosomes is affected by culture condition. We previously developed a serum-free, xeno-free and chemically defined medium, and umbilical cord-derived MSCs in this medium retained the immunosuppressive capability.METHODS: In this study, we evaluated the immunosuppressive function of exosomes from MSCs (MSC-Exo) in defined medium and their therapeutic effect on treating colitis.RESULTS AND CONCLUSIONS: In vitro studies indicated that MSC-Exo reduced the concentration of pro-inflammatory cytokines IFN-γ, TNF-α and IL-1β, and increased the secretion of anti-inflammatory cytokines TGF-β1 and IL-10, but no significant change of inhibitory effect on peripheral blood mononuclear cells proliferation was shown. In vivo experimental colitis showed that administration of MSC-Exo was able to significantly ameliorate the disease activity index score, weight loss, colon shortening, and the histological colitis score through up-regulation anti-inflammatory responses and down-regulation of inflammatory responses. Moreover, the use of MSC-Exo (200 μg) led to an improved therapeutic efficacy when compared with MSCs at a dose of 1×10⁶ cells. Our findings indicate that the exosomes from MSCs in defined medium possess a certain degree of immunosuppressive effect in vitro and exhibit a therapeutic capability in a mouse model of DSS-induced colitis through suppressing inflammation mechanism.

Experimental Research of Immunosuppressive Effect of Sinomenine on Skin Transplantation / 中国药师

Objective: To investigate the immunosuppressive effect of sinomenine (SIN) on xenogenic skin transplantation in mice.Methods: BALB/c→C57BL/6 tergal skin transplantation model was established by an operation, and then the mice were divided into 5 groups at random, namely sham group, model group, SIN group (30 mg·kg-1), ciclosporin A group (CsA) (10 mg·kg-1) and combination of SIN and CsA group (SIN 30 mg·kg-1 and CsA 5 mg·kg-1) (n=10).All the mice were intraperitoneally administered once a day for ten days.The survival days of skin graft were recorded, and the IL-2 levels in plasma were determined by ELISA respectively on the 4th and 8th day after the operation.Results: The mean survival days of skin graft in the groups treated with different drugs were significantly prolonged when compared with that in the model group (P<0.01).The combination of SIN and CsA administration showed longer mean survival days than SIN or CsA (P<0.05 or P<0.01).The IL-2 levels in plasma in the groups treated with different drugs were significantly reduced than those in the model group on the 4th and 8th day after the operation (P<0.01).Conclusion: SIN may have a good immunosuppressive effect in the mice with xenogenic skin transplantation, and the combination of SIN and CsA shows a synergistic effect.

Immunosuppressive effect of curcumin on skin transplantation in mice / 药物评价研究

Objective To investigate the immunosuppressive effect ofcurcumin on xenogenic skin transplantation in mice.Methods The skin transplantation model was established by an operation,tergal skin flaps from BALB/c donor mice transplanted to the back of C57BL/6 recipient mice.Then recipient mice were divided into five groups at random,namely sham,model,curcumin (50 mg/kg),Cyclosporin A (10 mg/kg) and curcumin + Cyclosporin A (50 mg/kg + 5 mg/kg).All mice were ip administered once daily for 10 d.The survival days of skin graft were recorded in all groups.The interleukin-2 (IL-2) levels in plasma of all mice were determined by ELISA 4 and 8 d after the operation,respectively.Results The mean survival time of skin graft in curcumin,Cyclosporin A and curcumin + Cyclosporin A groups were 14.77,16.81 and 19.96 d,respectively,which showed significant.differences comparing with 12.10 d of model group (P ＜ 0.01).Combination of curcumin and Cyclosporin A administration showed a longer mean survival days than curcumin or Cyclosporin A group (P ＜ 0.05 or 0.01).The IL-2 levels in plasma of mice in curcumin,Cyclosporin A and curcumin + Cyclosporin A groups on postoperative day 4 were 3.68,2.05 and 2.70 ng/mL,respectively,which were significantly reduced than 4.76 ng/mL of model group (P ＜ 0.05 or 0.01).The IL-2 levels in plasma of mice in curcumin,Cyclosporin A and combination of curcumin and Cyclosporin A groups on postoperative day 8 were 4.06,2.11 and 2.95 ng/mL,respectively,which were significantly reduced than 5.85 ng/mL of model group (P ＜ 0.01).Conclusion Curcumin may have a good immunosuppressive effect on mice with xenogenic skin transplantation.

Immunosuppressive effect of curcumin on skin transplantation in mice / 药物评价研究

Objective To investigate the immunosuppressive effect ofcurcumin on xenogenic skin transplantation in mice.Methods The skin transplantation model was established by an operation,tergal skin flaps from BALB/c donor mice transplanted to the back of C57BL/6 recipient mice.Then recipient mice were divided into five groups at random,namely sham,model,curcumin (50 mg/kg),Cyclosporin A (10 mg/kg) and curcumin + Cyclosporin A (50 mg/kg + 5 mg/kg).All mice were ip administered once daily for 10 d.The survival days of skin graft were recorded in all groups.The interleukin-2 (IL-2) levels in plasma of all mice were determined by ELISA 4 and 8 d after the operation,respectively.Results The mean survival time of skin graft in curcumin,Cyclosporin A and curcumin + Cyclosporin A groups were 14.77,16.81 and 19.96 d,respectively,which showed significant.differences comparing with 12.10 d of model group (P ＜ 0.01).Combination of curcumin and Cyclosporin A administration showed a longer mean survival days than curcumin or Cyclosporin A group (P ＜ 0.05 or 0.01).The IL-2 levels in plasma of mice in curcumin,Cyclosporin A and curcumin + Cyclosporin A groups on postoperative day 4 were 3.68,2.05 and 2.70 ng/mL,respectively,which were significantly reduced than 4.76 ng/mL of model group (P ＜ 0.05 or 0.01).The IL-2 levels in plasma of mice in curcumin,Cyclosporin A and combination of curcumin and Cyclosporin A groups on postoperative day 8 were 4.06,2.11 and 2.95 ng/mL,respectively,which were significantly reduced than 5.85 ng/mL of model group (P ＜ 0.01).Conclusion Curcumin may have a good immunosuppressive effect on mice with xenogenic skin transplantation.

Comparison of Immune Responses Induced by Deferoxamine and Deferasirox / 대한혈액학회지

BACKGROUND: The iron chelating agents (ICA) have various biological effects besides iron chelation. We investigated the immunomodulatory effects of Deferasirox (DFS) compared to Deferoxamine (DFO). METHODS: Spleen cells (SP) were obtained from 5 week-old C57/BL6 (H-2(b)). The cytotoxicity of ICAs was examined using the CCK8 method. For the cell proliferation assay, SP were cultured with irradiated in addition to 10, 50, 100micrometer of DFS or DFO and 200ng/mL of cyclosporin A (CSA). Cytokines and nitrite levels were evaluated from supernatants by ELISA. RESULTS: The viability of ICA was reported to be over 100%. Both DFS and DFO inhibited cell proliferation in a manner comparable to CSA. Cell proliferation without iron was reduced at the concentration of 100micrometer of DFO. With iron treatment, the reduction of the stimulation index was dependent on DFO concentrations. DFS decreased the proliferation without reference to the concentrations. After stimulation of phytohemagglutinin, the nitrite concentrations increased with iron. With lipopolysaccharides, the nitrite levels were higher in DFO with iron than control, but similar in DFS regardless of iron treatment. The levels of interleukin-2 were not different. Interleukin-10 was more abundantly produced in 50micrometer of DFO compared to DFS. Transforming growth factor-beta was higher in DFS than DFO at the low concentration, but opposite at the high concentration. CONCLUSION: These data suggested that both iron chelating agents possessed immune suppressive effects comparable to CSA. The immunosuppressive effect of DFS may be distinct from DFO. More experiments are required to determine the exact mechanism of the immunosuppressive effect of DFS.

Effects of Serial Bathing in a Cold Spring on Immunological Parameters of Patients with Rheumatoid Arthritis. Supplements of the study on Kan no Jigoku Spa / 日本温泉気候物理医学会雑誌

Previously one of our colleagues reported that the serial bathing (twice a day for 3 weeks) in a cold spring, Kan-no-Jigoku (simple hydrogen sulfide spring of 14°C) resulted in clinical improvements for patients with rheumatoid arthritis (RA). In that study, the effect on immune functions was also investigated, since RA is characterized by immune abnormalities. The following results were obtained.<br>1. No change was observed in serum gamma globulin levels and hemolytic complement activities.<br>2. Rheumatoid factor titers after the latex fixation test were improved in 2 out of 8 cases, by 1-2 steps after 2 weeks of bathing.<br>3. Circulating immune complex levels, which were significantly higher initially, fell gradually during 3 weeks of bathing, but insignificantly.<br>4. OKT4T cells decreased significantly after 3 weeks of bathing, while OKT3 and OKT8T cells decreased insignificantly. The OKT4/OKT8 ratio was elevated slightly after serial bathing of 3 weeks.<br>5. Plasma prostaglandin E levels were elevated significantly after 2 weeks, but returned to the initial levels after 3 weeks of bathing, although all the levels were within normal range. No such changes of them were observed by a hot spring bathing.<br>6. Plasma cyclic AMP levels, which were a little higher than the normal range in 3 out of 9 cases initially, were also elevated significantly after 1 week of bathing and returned to the initial levels thereafter gradually, while no significant changes of them were observed by a hot spring bathing.<br>7. Urinary hydroxyproline excretion was not changed by the serial bathing.<br>From the above results it was suggested that a cold spring bathing may give an immunosuppressive effect to a living body, resulting in benefit for RA patients.