• Biomolecules & Therapeutics
• /
• 제17권1호
• /
• pp.43-46
• /
• 2009

The immunosuppressive properties of flavonoids were examined for the first time by testing their effects on T-cell-mediated antibody production, using a classical plague-forming cell (PFC) assay in mice. Among the tested flavonoids including naringenin, chrysin, flavonol, galangin, quercetin, morin, myricetin and biochanin A, only quercetin, orally administered at 25 mg/kg, significantly inhibited the number of IgMproducing PFCs induced by sheep red blood cells (SRBC). Interestingly, biochanin A (isoflavone) increased the number of PFCs, suggesting an immunostimulatory effect. The other flavonoids tested did not inhibit or enhance PFC response significantly. Quercetin was also found to show thymus atrophy dose-dependently at 5-500 mg/kg. All these results indicate that quercetin inhibits in vivo antibody production probably by inhibiting T-cell function.

• Journal of Pharmaceutical Investigation
• /
• 제28권4호
• /
• pp.241-247
• /
• 1998

Ketoconazole is an imidazole antifungal agent which inhibits the biosynthesis of fungal cellmembrane ergosterol and has immunosuppressive properties in vitro. Biphenyl dimethyl dicarboxylate (PMC) has been utilized for antioxidative action and for liver-protective purposes. Studies were undertaken to investigate effects of biphenyl dimethyl dicarboxylate (PMC) on the immunosuppression of ketoconazole in ICR mice. In the combination of PMC and ketoconazole, as compared with the treatment of ketoconazole alone, there were significant increases in activities of natural killer (NK) cells and phagocytes along with circulation leukocytes. The elevation of serum glutamic-pyruvic transaminase (S-GPT) and total protein levels caused by ketoconazole were reduced by the combination of PMC and ketoconazole. In addition, lower serum albumin and albumin/globulin (A/G) ratio were also increased to normal level.

• Biomolecules & Therapeutics
• /
• 제10권4호
• /
• pp.224-229
• /
• 2002

Triazine herbicide has been reported to directly suppress the immune response. In the present study, we examined various functions of murine peritoneal macrophages that were isolated and stimulated with LPS after simazine (300 and 600 mg/kg body weight), a triazine herbicide, was administered every day for 4 weeks. Simazine decreased the capacity of phagocytosis, compared to those of carboxymethylcellulose (CMC)-treated control group. In addition, the production of NO and TNF-$\alpha$ was decrcased in macrophages of simazinetreated mice. However, the production of hydrogen peroxide ($H_{2}O_{2}$) was not altered. In vitro tumoricidal activity of in vivo simazine-treated macrophages was reduced against target cell. B 16 melanoma. Taken together, these results suggested that simazine might have the immunosuppressive effect on macrophages after in vivo exposure, which was related to the reduction of tumoricidal activity.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.386.2-386.2
• /
• 2002

We investigated the effect of tectorigenin (1) with hypoglycemic and hypolipidemic effects on Phase I and II enzymes and TF activity to elucidate the action of an immunosuppressive compound (1) in the diabetic rat. Compound 1 was obtained from the hydrolysis of tectoridin easily isolated from the flower of Pueraria thunbergiana(Leguminosae). Puerariae Flos has been used as therapeutics for diabetes mellitus in traditional medicine of Korea. (omitted)

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.306.2-306.2
• /
• 2002

The main targets for the immunosuppressive calcineurin inhibitors. tacrolimus (FK-506) and cyclosporine A (CsA). have been considered to be activated T cells. but not antigen presenting cells (APCs). In the present study. we examined the effects of these drugs on the MHC-restricted presentation of exogenously added antigen. ovalbumin (OVA). in dendritic cells (DCs). Particulate form of OVA was efficiently captured. processed and presented on class I MHC molecules (cross-presentation) as well as on class II MHC molecules. (omitted)

• Childhood Kidney Diseases
• /
• 제27권1호
• /
• pp.1-10
• /
• 2023

Pediatric nephrotic syndrome (NS) is a clinical syndrome characterized by massive proteinuria, hypoalbuminemia, and generalized edema. Most childhood NS cases are idiopathic (with an unknown etiology). Traditional therapeutic approaches based on immunosuppressive agents largely support the key role of the immune system in idiopathic NS (INS), especially in the steroid-sensitive form. Although most previous studies have suggested the main role of T cell dysfunction and/or the abnormal secretion of certain glomerular permeability factors, recent studies have emphasized the role of B cells since the therapeutic efficacy of B cell depletion therapy in inducing and/or maintaining prolonged remission in patients with INS was confirmed. Furthermore, several studies have detected circulating autoantibodies that target podocyte proteins in a subset of patients with INS, suggesting an autoimmune-mediated etiology of INS. Accordingly, a new therapeutic modality using B cell-depleting drugs has been attempted, with significant effects in a subset of patients with INS. Currently, INS is considered an immune-mediated disorder caused by a complex interplay between T cells, B cells, soluble factors, and podocytes, which may vary among patients. More in-depth investigations of the pathogenic pathways of INS are required for an effective personalized therapeutic approach and to define precise targets for therapeutic intervention.

• Childhood Kidney Diseases
• /
• 제27권2호
• /
• pp.55-63
• /
• 2023

In 2021, a new chapter on the general management of glomerulonephritis (GN) was added to the Kidney Disease: Improving Global Outcomes (KDIGO). It emphasizes the importance of early general management of GN for improving long-term kidney outcomes and prognosis. The chapter introduces the management of glomerular diseases in 18 subchapters. Here, kidney biopsy for the diagnosis and evaluation of kidney function and the management of complications, such as hypertension, infection, and thrombosis, are presented. Moreover, the adverse effects of glucocorticoids and immunosuppressive therapy, which are commonly used drugs for glomerular disease, are mentioned, and a guideline for drug selection is presented. Each subtheme focused on items reflecting the interpretation of the "practice points" of the expert working group are introduced. In this review of the general treatment for GN in the KDIGO guidelines, excluding pregnancy and reproductive health, we focused on and compared various references pertaining to pediatric GN management.

• Childhood Kidney Diseases
• /
• 제21권1호
• /
• pp.35-39
• /
• 2017

Azathioprine is commonly used as immunosuppressive therapy for various inflammatory diseases including chronic glomerulonephritis. Myelosuppression is a common side effect of azathioprine, resulting in the need for dose reduction. However, severe pancytopenia or alopecia is not often encountered. Here, we report a case of severe myelosuppression, and alopecia totalis that occurred after azathioprine treatment in a patient with IgA nephropathy. A 10-year-old boy with IgA nephropathy was treated with oral deflazacort and later with azathioprine. After 4 weeks, the patient complained of hair loss, and despite a dose reduction in azathioprine, he developed bone marrow suppression and alopecia totalis in two weeks. The blood indices and alopecia of the patient had returned to normal after azathioprine withdrawal and 3 consecutive doses of granulocyte colony-stimulating factor. We suggest that physicians remain vigilant to the side effects of azathioprine. Unusual hair loss after azathioprine treatment might suggest a defect in the metabolism of the drug, warranting the discontinuation of azathioprine to prevent more severe side effects.

• Journal of Microbiology and Biotechnology
• /
• 제22권8호
• /
• pp.1066-1076
• /
• 2012

Previous observations demonstrated that various immunosuppressive agents and their combination therapies can increase allograft survival rates. However, these treatments may have serious side effects and cannot substantially improve or prolong graft survival in acute graft-versus-host disease (GVHD). To improve the therapeutic potency of divalent immunoadhesins, we have constructed and produced several tetravalent forms of immunoadhesins comprising each of cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), CD2, and lymphocyte activation gene-3 (LAG3). Flow cytometric and T cell proliferation analyses displayed that tetravalent immunoadhesins have a higher binding affinity and more potent efficacy than divalent immunoadhesins. Although all tetravalent immunoadhesins possess better efficacies, tetravalent forms of CTLA4-Ig and LAG3-Ig revealed higher inhibitory effects on T cell proliferation than tetravalent forms of TNFR2-Ig and CD2-Ig. In vitro mixed lymphocytes reaction (MLR) showed that combined treatment with tetravalent CTLA4-Ig and tetravalent LAG3-Ig was highly effective for inhibiting T cell proliferation in both human and murine allogeneic stimulation. In addition, both single tetravalent-form and combination treatments can prevent the lethality of murine acute GVHD. The results of this study demonstrated that co-blockade of the major histocompatibility complex class (MHC)II:T cell receptor (TCR) and CD28:B7 pathways by using tetravalent human LAG3-Ig and CTLA4-Ig synergistically prevented murine acute GVHD.

• 대한본초학회지
• /
• 제21권4호
• /
• pp.93-101
• /
• 2006

Objectives : Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease(AD), Parkinson's disease(PD) and Huntington's disease(HD) in the inflammatory process. Uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines ($TNF-{\alpha}$, $IL-1{\beta}$ and IL-6), NO, PEG2 and superoxide. In this study, the immunomodulatory effects of the herbal extract Panax notoginseng on cultured BV2 microglial cells and primary microglia were investigated to address potential therapeutic or toxic effects. Notoginseng radix extracts extracted from the root of the plant using Methanol. Methods : Cells were stimulated with LPS and treated with notoginseng at different concentrations. Results : Notoginseng significantly decreased LPS-induced production of $TNF-{\alpha}$ and IL-6 by the cultured microglial cells in a dose-dependent manner. The activation of iNOS mRNA and secretion of nitric oxide(NO) in microglial cells were inhibited in microglial cells in a dose-dependent manner by notoginseng. Conclusion : These results indicate that notoginseng inhibits LPS-induced activation of microglial cells and demonstrates notoginseng possess anti-inflammatory and immunosuppressive properties in vitro.