Objective To explore effects of several immunosuppressants on cytokine expressions after repair for a sciatic nerve injury in a rat model. Methods The sciatic nerves of 42 rats were cut and suturedend to end. After operation, the rats were divided into 6 groups. Group A(n=9) was served as a control with no medicines given. Group B (n=9) was given methylprednisolone 20 mg/(kg·d) for 2 days. Groups C(n=9) and D(n=3) were given FK506 1 mg/(kg·d) for 2 weeks and 4 weeks respectively, and were given the same doses of methylprednisolone as Group B. Groups E and F were given CsA 2 mg/(kg·d) for 2 weeks and 4 weeks respectively, and were given the same doses of methylprednisolone as Group B. The sciaticnerves were sampled at 1, 2 and 4 weeks postoperatively. And immuneohistochemistry stainings of interleukin 1β(IL-1β)， tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and macrophage migration inhibitory factor(MIF) were performed. The staining results were compared and analyzed. Results The expression peaks of IL-1β and IFN-γ were found at the 1st week postoperatively in Group A. Then, the expression decreased rapidly at the 2nd week and disappeared at the 4th week. As for TNF-α and MIF, they were only found to have a low expression until the 1st week in Group A. In groups C-F, the expression peaks of IL-1β, TNF-α and IFN-γ were found at the 2nd week, while the expression peak of MIF was still at the 1st week, and the expression of all the cytokines extended to the 4th week. The expressions of these cytokines in Group B were just between the expression levels of Group A and Groups C-F. Conclusion Immunosuppressants can delay the expression peaks and significantly extend the expression time of IL-1β, TNF-α, IFN-γ and MIF after repair for a sciatic nerve injury in a rat model.
Drugs may induce hepatitis B virus (HBV) reactivation (HBV-R). Here we have reviewed the definition and harm of HBV-R, the risk drugs and their underlying mechanism, the influence factors, as well as the early intervention measures. It is shown that multiple drugs, including chemotherapy drugs, immunotherapy drugs, directly acting antivirals, cell therapy, etc., can induce HBV-R by affecting host immunity or directly activating HBV transcription factors. HBV-R could cause severe liver damage, even interruption of treatment of original diseases, affecting the prognosis of patients. Through precisely identifying risk drugs, monitoring the influence factors, and prescribing preventive anti-HBV regimen if necessary, the incidence of HBV-R can be significantly reduced. It is also suggested that clinical physicians should not only pay attention to the early identification and intervention of HBV-R, but also further study the mechanism of HBV-R in depth, especially the underlying mechanism between host, HBV and risk factors. This will help to promote the discovery of more valuable markers for risk prediction and targets for early intervention, and to further reduce the risk of HBV-R and improve the prognosis of patients.
The corticosteroids are the firstline therapeutical agents for noninfectious uveitis patients, but systemic corticosteroids are ineffective for some chronic or recurrent patients, and have many long term usagerelated side effects; these patients may need treatment of immunosuppressive agents and/or biologic agents. However, the mechanism, indication, efficacy and sideeffects of each type of the immunosuppressive agents or biologic agents are not identical. In clinical practice, we should use different and sensitive immunosuppressive agents or biologic agents for different types of uveitis, and watch their efficacy and toxic effects closely. In order to improve the effectiveness of the treatment, the classification, efficacy and existing concerns of commonly used uveitis drugs need to be further clarified.
ObjectiveTo study the immunogenicity of human bone marrow mesenchymal stem cells (BMSCs) and the suppression ability to the proliferation of peripheral blood mononuclear cell (PBMC) during osteogenic, chondrogenic, and adipogenic differentiations. MethodsBMSCs were isolated from bone marrow of healthy donors and were induced to osteogenic, chondrogenic, and adipogenic differentiations for 7, 14, and 21 days. The expressions of human leukocyte antigen (HLA) class I and class II were detected by flow cytometry. PBMC were isolated from peripheral blood of healthy donors and were co-cultured with BMSCs at a ratio of 10∶1 for 5 days. The suppression ability of undifferentiated and differentiated BMSCs to proliferation of PBMC were detected by flow cytometry. ResultsThe HLA class I expression was observed but almost no expression of HLA class II was seen in undifferentiated BMSCs. There was no obviously change of the HLA class I and class II expressions during osteogenic and chondrogenic differentiations (P>0.05), and a low expression of HLA class II was kept. The HLA class I expression gradually increased at 14 and 21 days after adipogenic differentiation, showing significant differences when compared with the value at 0 and 7 days (P<0.05);the HLA class II expression also gradually increased at 7, 14, and 21 days after adipogenic differentiation, showing significant differences when compared with the value at 0 day (P<0.05). There was no proliferation of PBMC without the stimulation of CD3 and CD28 microspheres and significant proliferation was observed when CD3 and CD28 microspheres were added, and undifferentiated BMSCs could significantly inhibit the proliferation of PBMC. There was no obvious change of the ability of BMSCs to inhibit the proliferation of PBMC during osteogenic and chondrogenic differentiations (P>0.05);and the ability of BMSCs to inhibit the proliferation of PBMC was gradually weakened at 7, 14, and 21 days after adipogenic differentiation, showing significant differences among different time points (P<0.05). ConclusionBMSCs maintain low immunogenicity and strong immune suppression ability during osteogenic and chondrogenic differentiations, which are suitable for allogenic tissue engineering repair and cell transplantation. However, increased immunogenicity and decreased immune suppression ability after adipogenic differentiation may not be suitable for allogenic tissue engineering repair and cell transplantation.
Objective To summarize the significance of CYP3A5 in individualized immunosuppressive treatment with tacrolimus (FK506) after liver transplantation. Methods Relevant literatures about the effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in liver transplant recipients, which were published recently domestic and abroad, were reviewed and analyzed. Results Tacrolimus was used effectively to prevent allograft rejection after liver transplantation. Narrow therapeutic range and individual variation in pharmacokinetics made it difficultly to establish a fixed dosage for all patients. Genetic polymorphism in drug metabolizing enzymes and in transporters influenced the plasma concentration of tacrolimus. CYP3A5 genotype had an effect on the tacrolimus dose requirement in liver transplant recipients.Conclusion Genotyping for CYP3A5 may help optimal individualization of immunosuppressive drug therapy for patients undergoing liver transplantation