• Journal of Microbiology and Biotechnology
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• 제28권10호
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• pp.1716-1722
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• 2018

Immunosuppressive drugs are used to make the body less likely to reject transplanted organs or to treat autoimmune diseases. In this study, five immunosuppressive drugs including two glucocorticoids (dexamethasone and prednisolone), one calcineurin inhibitor (cyclosporin A), one non-steroid anti-inflammatory drug (aspirin), and one antimetabolite (methotrexate) were tested for their effects on viral proliferation using feline foamy virus (FFV). The five drugs had different cytotoxic effects on the Crandell-Ress feline kidney (CRFK) cells, the natural host cell of FFV. Dexamethasone-pretreated CRFK cells were susceptible to FFV infection, but pretreatment with prednisolone, cyclosporin A, aspirin, and methotrexate showed obvious inhibitory effects on FFV proliferation, by reducing viral production to 29.8-83.8% of that of an untreated control. These results were supported by western blot, which detected viral Gag structural protein in the infected cell lysate. As our results showed a correlation between immunosuppressive drugs and susceptibility to viral infections, it is proposed that immune-compromised individuals who are using immune-suppressive drugs may be especially vulnerable to viral infection originated from pets.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.145-151
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• 2012

In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured $in$ $vivo$ phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its $in$ $vivo$ PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions.

• 대한수의학회지
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• 제38권4호
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• pp.811-817
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• 1998

Humoral and cellular immune responses are depressed in chickens infected with reticuloendotheliosis virus(REV). The extent of depression is influenced by the age of infection and strain of virus. This study was conducted for investigation of immunosuppressive effects of a Korean isolate of REV. Chickens infected with REV-HI, a Korean isolate, at 1 day old were severely suppressed in the vaccinal immunity against Newcastle disease, infectious bronchitis and infectious bursal disease. But these immunosuppressive effects were not observed in chickens infected with the virus at 2 weeks of age, or contact infected by growing in-contact with inoculated chickens from one day old. The clinical signs following infectious laryngotracheitis(ILT) vaccination in chickens infected with REV-HI at 1 day old were more severe than those of uninfected chickens, and some of REV-infected chickens(21.4%) were died after the vaccination. Mortality following virulent ILT virus infection was increased in REV-HI infected chickens. Effects of REV infection at one day old to susceptibilities to subsequent Chicken anemia agent (CAA) infection were also studied. Chickens were infected with REV-HI at 1 day old and subsequently inoculated CAA at 1, 7, 14 and 28 days old, respectively. Mortalities of the chickens infected with REV-HI and subsequent CAA infection were 100, 100, 40 and 0%, respectively, whereas 23, 8, 0 and 0% of chickens infected with only CAA were died, respectively. These above all results suggest that a Korean isolate of REV may be highly immunosuppressive.

• Journal of Microbiology and Biotechnology
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• 제26권3호
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• pp.567-571
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• 2016

We investigated the increased risk of Clostridium difficile infection (CDI) caused by the combined use of antibiotics and an immunosuppressive drug in a mouse model. Our data showed that an approximate return to pretreatment conditions of gut microbiota occurred within days after cessation of the antibiotic treatment, whereas the recovery of gut microbiota was delayed with the combined treatment of antibiotics and dexamethasone, leading to an increased severity of CDI. An alteration of gut microbiota is a key player in CDI. Therefore, our data implied that immunosuppressive drugs can increase the risk of CDI through the delayed recovery of altered gut microbiota.

• Annals of Clinical Neurophysiology
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• 제9권2호
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• pp.51-58
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• 2007

Autoimmune myasthenia gravis (MG) is the neuromuscular junction disorder mostly caused by antibody against the acetylcholine receptor (AChR antibody) at the muscle endplate. The goal of treatment is to induce and maintain remission, i.e., absence of symptoms, with the least cost-to-benefit ratio. Although corticosteroids are effective in inducing remission in most patients, they have numerous potentially serious adverse effects with their long-term use. In addition, some patients do not respond or are intolerant to the conventional treatment. In this article, we discuss the difficulties encountered in long-term immunosuppressive treatment of MG, and review useful tips for the use of corticosteroids. Long-term immunosuppressive agents that can be used in steroid-refractory or -dependent patients will be reviewed with their safety profiles and efficacy in MG.

• Biomolecules & Therapeutics
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• 제13권2호
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• pp.65-77
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• 2005

Present article reviews about clinical pharmacology of mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), as widely used component of immunosuppressive regimens in the organ transplantation field. MMF, used alone or concomitantly with cyclosporine or tacrolimus, has approved in reducing the incidence of acute rejection and has gained widespread use in solid organ such as kidney, heart and liver transplantation. The application of MPA and development of MMF has shown a considerable impact on immunosuppressive therapy for organ transplantation as a new immunosuppressive agent with different mechanism of action from other drugs after early 1990s. In particular aspect, use of MMF, a morpholinoethyl ester of MPA, represented a significant advance in the prevention of organ allograft rejection as well as allograft and patient survival. In considering MMF clinical data, it is important to note that there is a strong correlation between high MPA area under curve(AUC) values and a low probability of acute allograft rejection. Individual trials have shown that MMF is generally well tolerated and revealed that MMF decreased the relative risk of developing chronic allograft rejection compared with azathioprine. Recent clinical investigations suggested that improved effectiveness and tolerability will results from the incorporation of MPA therapeutic drug monitoring into routine clinical practice, providing effective MMF dose individualization in renal and heart transplant patients. Therefore, MMF has a selective immunosuppressive effect with minimal toxicity and has shown to be more effective that other agents as next step of immunosuppressive agents and regimens that deliver effective graft protection and immunosuppression along with a more favorable side effect.

• 농업과학연구
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• 제13권2호
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• pp.299-310
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• 1986

3M KCl을 이용하여 면양 squamous cell carcinoma 및 정상면양 조직(組織)에서 획득(獲得)한 추출액(抽出液)의 성상을 sephadex column chromatography, lymphocyte blastogenicity assay, acid dissociation method 및 gradient polyacrylamide gel electrophoresis 등을 이용하여 연구하였다. Sephadex column chromatography에서 얻은 5개의 종양분획(腫瘍分劃)중 분획(分劃)III은 가장 종양특이(腫瘍特異)한 항원(抗原)을 보유하고, 분획(分劃)V lymphocyte reactivity를 저하(低下)시키는 성분을 함유하고 있었다. 각 분획(分劃)을 분자량(分子量) > 100,000, 10,000~100,000 및 < 10,000의 3군(群)으로 분리한 바 종양특이항원(腫瘍特異抗原) 및 면역저지물질(免疫沮止物質)은 10,000~100,000분획(分劃)에서 나타났다. 분획(分劃)I tumour specific antigen - antibody complex를 내포하고 있음이 밝혀졌다. Gradient gel electrophoresis를 이용하여 분획(分劃)을 더욱 세분했을 때 분획(分劃)III은 Slice No 4~6에서 종양특이물질(腫瘍特異物質)이 인정되었고, 분획(分劃)V Slice No 9~11에서 면역기능저하물질(免疫機能低下物質)이 있음이 밝혀졌다.

• 동의생리병리학회지
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• 제28권5호
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• pp.499-505
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• 2014

Immunosuppressors cyclosporine A(CsA) and tacrolimus(FK506), the primary cellular target of which is calcineurin/nuclear factor of activated T cells(NFAT) signalling pathways, decrease beta-cell insulin content and mRNA expression. The posttransplantation diabetes mellitus(PTDM) is a frequent complication in immunosuppressive therapy. The present study was to examine the effect of a crude water extracts of medicinal herbs such as Sanguisorba officinalis(SOE) on the immunosuppressive activity with lymphocyte and insulin secretion in insulinoma cell lines with RIN-5mF. It was found that SOE treatment had effect of immunosuppressor on lymphocytes and also significantly increased insulin secretion in RIN-5mF compared to other agents. we might suggest a mechanism on insulin secretion by HNF4a. Taken together, the present study suggested that SOE might serve as immunosuppressive drug in PTDM.

• Clinical and Experimental Pediatrics
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• 제48권5호
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• pp.476-480
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• 2005

Immunosuppressive therapy in pediatric renal transplant recipients is changing consequence of the increasing number of available immunosuppressive agents. The optimal use of immunosuppressive agents requires a thorough understanding of the pharmacokinetic characteristics, but the information on the pharmacokinetic characteristics of these drugs in pediatric transplant recipients is still limited. In general, patients younger than 5 years old show higher clearance rates, therefore the need for higher dosages in younger patients seems evident. By the therapeutic drug monitoring, trough($C_{min}$) and peak level($C_{max}$) are measured and the area under the blood concentration-time curve(AUC), which is taken as being representative of total systemic exposure can be calculated. Cyclosporine A (CSA) has poor bioavailability, which contributes to high inter- and intra-patient pharmacokinetic variability. CSA concentration measured 2 hours after administration($C_2$) has better correlation with the AUC than $C_{min}$ and is an alternative technique that predicts the AUC. Tacrolimus(Tac) has a great deal of inter-individual variability like CSA but intra-individual variability in systemic exposure is considered to be low. Both CSA and Tac are metabolized by a cytochrome P-450 enzyme isoform(CYP3A4). We should consider changing the dosages when CSA or Tac is used in combination with the medicines that inhibit or induce the CYP3A4. In case of steroid-free immunosuppressive therapy, the blood concentration of Tac should be frequently checked and dosage adjustment may be needed.

• Journal of Oral Medicine and Pain
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• 제42권1호
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• pp.20-24
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• 2017

Drug-induced gingival overgrowth (DIGO) is an adverse drug reaction mainly described with three types of commonly prescribed drugs, namely, calcium channel blockers (CCBs) (nifedipine, diltiazem, and verapamil), anti-convulsants (phenytoin), and immunosuppressive agents (cyclosporine). Numerous reports have associated gingival overgrowth with the newer generation of immunosuppressive agents (tacrolimus, sirolimus, and everolimus), and CCBs (amlodipine, felodipine, nicardipine, and manidipine). Especially, patients concomitantly medicated with an immunosuppressive agent and CCB have a higher DIGO chance. Dentists need to be aware of drugs that induce gingival overgrowth, the possibility of DIGO, and risk factors, and also prevent the progression of DIGO by early detection of DIGO, consultation about the drug change, and the maintenance of strict dental hygiene regimes.