SEARCH · PubMed Health

Results for “IMMUNOSUPPRESSIVE AGENTS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources

PubMed1990

Immune response of mallard ducks treated with immunosuppressive agents: antibody response to erythrocytes and in vivo response to phytohemagglutinin-P.

The ability of two in vivo tests to assay immune competence of mallard ducks (Anas platyrhynchos) treated with various immunomodulatory agents was examined. Skin responses to phytohemagglutinin-P (PHA-P) injected intradermally and serum antibody levels produced in response to sheep red blood cells (SRBC) were measured. As measured by the skin response to PHA-P, ducks injected intramuscularly with cyclophosphamide or cyclosporine did not respond differently from control-injected ducks. Dexamethasone injected intramuscularly significantly suppressed the skin response to PHA-P. As measured by antibody levels in response to SRBC, ducks injected intramuscularly with cyclophosphamide responded with antibody titers similar to controls. Cyclosporine injected intramuscularly reduced the level of immunoglobulin (Ig) G significantly in one of two experiments. Dexamethasone injected intramuscularly reduced peak total and IgG titers. These experiments provide information on the viability of these two in vivo tests to reflect immune competence of mallard ducks.

Animals↗

PubMed1978

Enhancement and inhibition of immunological mechanisms by immunosuppressive agents. I. Dose effect on priming and generation of memory to a bacterial antigen.

A new experimental system is described which allows the study of the effect of immunosuppressors upon the priming and generation of memory to an antigen from Escherichia coli. A single dose of bacterial beta-D-galactosidase without adjuvant injected into C57B1/6J mice primes and elicits memory but not antibodies. Thus by administering immunosuppressors near the priming injection, one can examine whether primary antibody formation is enhanced and whether priming generation of memory is enhanced or inhibited. We found that X-rays, cyclophosphamide and oxisuran (2-[(methylsulfinyl)acetyl]pyridine) either enhance or inhibit the elicitation of memory, depending on dosage, although they do not alter primary antibody unresponsiveness. The data show two main features: (a) immunosuppressors can enhance immunization; and (b) generation of memory can be improved without increasing antibody levels. The former finding draws attention to the role that immunosuppressors might play in the breaching of tolerance to self-antigens which share determinants with microbes, while the latter observation shows that antibody synthesis and elicitation of memory can follow independent pathways.

Animals↗

PubMed2000

Comparison between tacrolimus and cyclosporine as immunosuppressive agents compatible with tolerance induction by CD4/CD8 blockade.

BACKGROUND: Donor-specific tolerance can be induced in mice by transient antibody blockade of the CD4 and CD8 co-receptors of T cells. To evaluate the potential application of CD4/CD8 blockade in the clinic, we have asked if either tacrolimus or cyclosporine counteract the tolerogenic process. METHODS: Using the fully mismatched mouse cervical heart transplant model, BALB/c (H2d) to CBA (H2k), the experimental groups were (i) no therapy, (ii) tacrolimus (1 mg/kg, i.p., daily, days 0-14); (iii) cyclosporine (25 mg/kg, i.p., daily, days 0-14), (iv) blocking monoclonal antibodies (mAbs) to CD4 and CD8 (2 mg, i.p., starting day 0 and on alternating days thereafter for a total of six doses), (v) tacrolimus plus mAbs, and (vi) cyclosporine plus mAbs. RESULTS: Allograft survival was prolonged in both the tacrolimus and cyclosporine groups. mAbs alone induced tolerance, and mAbs combined with tacrolimus also induced tolerance. In contrast, the combination of mAbs and cyclosporine was toxic. CONCLUSIONS: The induction of tolerance by blocking CD4 and CD8 was not prevented by tacrolimus. However, combination of cyclosporine with the same tolerogenic protocol was toxic to mice.

Animals↗

PubMed1997

An immunosuppressive agent, FTY720, increases intracellular concentration of calcium ion and induces apoptosis in HL-60.

We previously reported that FTY720 is an efficient inducer of apoptosis in lymphocytes and cultured cell lines. In the present study, HL-60 human promyerocytoma cells also induced apoptosis through in vitro treatment with the drug, demonstrating extensive DNA fragmentation 6 hr after incubation. The major target of FTY720 was the common signalling pathway of apoptosis, since a rapid (< 1 min) increase in the intracellular Ca2+ concentration ([Ca2+]i) was found in the cells treated with the drug. Calcium chelation in the culture medium with EGTA did not affect the [Ca2+]i mobilization. A phospholipase C inhibitor, U73122, inhibited the increase in [Ca2+]i as well as the fragmentation of the nuclear DNA, whereas U73343, a non-effective analogue of U73122, had little effect. These results suggest that FTY720-induced apoptosis is mediated through an activation of phospholipase C and the subsequent release of Ca2+ from intracellular calcium pools. In addition, the treatment of HL-60 with pertussis toxin (PTX) did not inhibit Ca2+ mobilization or apoptosis, suggesting that the activation of phospholipase C is independent of PTX-sensitive G-proteins.

Apoptosis↗

PubMed2001

[Pharmacological profiles of mycophenolate mofetil (CellCept), a new immunosuppressive agent].

Mycophenolate mofetil (MMF, CellCept), a semisynthetic derivative of mycophenolic acid (MPA) produced by a fungus, is an inhibitor of the inosine monophosphate dehydrogenase (IMPDH) enzyme (IC50 = 25 nM) that catalyzes the synthesis of guanosine monophosphate (GMP) from inosine. GMP is an essential nucleoside for purine synthesis during cell division. As T and B-lymphocytes almost exclusively use the de novo pathway of purine synthesis, these cells are particularly sensitive to the inhibitory action of MMF. It has a mechanism of action distinct from cyclosporine and tacrolimus. Although MMF does not affect cytokine production, by inhibiting the rate-limiting enzyme IMPDH in the de novo synthesis of purines, it inhibits the proliferation of T and B-lymphocytes, the production of antibodies, and the generation of cytotoxic T lymphocytes. Reversal of acute allograft rejection and increased survival of kidney, heart and bone marrow cell allograft has been shown in several animal studies. Moreover, it was suggested that MMF combined with CsA prevented the acute rejection, and approximately half of the animals became long-term survivors. The Ministry of Health and Welfare approved MMF in 1999 for use for rejection treatment in renal transplantation based on several prospective, randomized and blind efficacy trials.

Animals↗

PubMed1975

The effect of various immunosuppressive agents on mouse peritoneal macrophages and on the in vitro phagocytosis of Escherichia coli O4:K3:H5 and degradation of 125I-labelled HSA-antibody complexes by these cells.

Large doses of hydrocortisone, cyclophosphamide, and methotrexate injected subcutaneously, and whole-body irradiation (500 rads) caused a reduction in the number of peritoneal cells (PE cells) obtained after intraperitoneal injection of the treated mice with proteose-peptone. The same dose of cyclophosphamide and irradiation induced morphological changes in PE macrophages. There were more giant cells in the peritoneal exudates from treated mice as compared to control mice. 'Pharmacological' and larger doses of hydrocortisone, methotrexate and azathioprine or anti-lymphocyte globulin had no effect on the in vitro phagocytic capacity of proteose-peptone-stimulated mouse PE macrophages. This also applied to doses of up to 50 mg/kg of cyclophosphamide. In contrast, whole-body irradiation (500 rad) and 100 mg/kg of cyclophosphamide decreased the phagocytic capacity of mouse macrophages in vitro and reduced the ability of PE cells to degrade 125I-labelled HSA-antibody complexes in vitro. The greatest effect was noted 4-5 days after whole-body irradiation or four to five subcutaneous injections of cyclophosphamide.

Animals↗

PubMed1996

A pharmacokinetic study of intravenous CTLA4Ig, a novel immunosuppressive agent, in mice.

Three skin-intact mice in each group received a single 0.07-, 0.29-, or 0.57-mg dose of CTLA4Ig intravenously (i.v.). Three skin-grafted mice received a single 0.29-mg dose i.v. and another three skin-grafted mice received a 0.29-mg dose once daily for 7 days (the dose was administered via the tail vein). Serial blood samples (0.15 mL) were obtained by retro-orbital bleeds up to 240 h after all single doses and up to 360 h after the last multiple dose. Serum samples were analyzed for CTLA4Ig by a validated enzyme immunoassay method. The concentration data were subjected to noncompartmental pharmacokinetic analysis. Both Cmax and AUCinf values increased in a dose-proportional manner in skin-intact mice. The CLT values were dose independent. The MRT, t1/2, and Vdss values at the 0.07-mg dose level were significantly lower than those obtained for both the 0.29- and 0.57-mg dose levels; however, the respective values between the 0.29- and 0.57-mg dose levels were not significantly different. No significant differences were found in the pharmacokinetic parameters between the skin-intact and skin-grafted mice.

Abatacept↗

PubMed1997

Induction of IL-5 expression by IL-2 is resistant to the immunosuppressive agents cyclosporin A and rapamycin.

T cell cytokine expression may be induced by the cytokine IL-2 or via the TCR complex. The comparative effects of cytokine- and TCR-mediated signalling on the induction of human IL-5 mRNA were examined. Cytokine mRNA expression was analysed by RT-PCR in fresh peripheral blood mononuclear cells (PBMC) from normal individuals and in populations of activated T lymphocytes, derived from phytohaemagglutinin (PHA)-stimulated PBMC. rIL-2 induced IL-5 expression in PBMC, the kinetics of which were similar to the effects of PHA. rIL-4 induced IL-5 mRNA expression in activated T lymphocytes. IL-5 expression induced by either IL-2 or PHA was completely abolished by the protein synthesis inhibitor cycloheximide. rIL-2-induced IL-5 expression was resistant to cyclosporin A (CsA), whereas IL-5 expression elicited by PHA was inhibited by CsA, at doses as low as 10 ng/ml. Rapamycin (RAP) had no effect on rIL-2-stimulated IL-5 expression, but suppressed IL-5 expression induced by PHA. The inhibitory effect of RAP on PHA-induced IL-5 expression was more apparent at 12 and 24 h after stimulation than at earlier times. The resistance of IL-2 receptor (IL-2R) signalling to CsA and RAP indicates that the IL-2R and the TCR are associated with different pathways regulating IL-5 expression.

Adjuvants, Immunologic↗

PubMed1989

[Classical immunosuppressive agents].

Immunodepressive or immunoregulatory drugs might be indicated among the therapeutic possibilities in uveitis and associated diseases, especially in those cases, which resist to specific treatment and steroids, and in those in which disorders of the immune system play a pathogenetic role. Classical cytostatic drugs mainly act by a reduction of the amount of circulating lymphocytes. The most useful seem to be the alkylating drugs (chlorambucil, cyclophosphamide) and antimitotics (procarbazine, colchicine), or antifolic (methotrexate), while the antipurines (azathioprine) seem to us less effective. Such therapy requires the full consent of the patient. The dosage of the drug has to be well established in order to keep the total amount of leucocytes between 4,000-5,000/mm3. Side effects can be hair loss, sterility, rarely hemorrhagic cystitis, and, mostly only in the initial therapy period, nausea and vomiting. Teratogenic risks seem non-existent. Since the therapeutical effect comes rather slowly, a local steroid therapy can be added. Absolute indications for such therapy are Behçet and sympathetic ophthalmitis, while all severe chronic uveitis forms are relative indications. Acute iritis and chorioretinitis are contraindications. The results with procarbazine and cyclophosphamide run around 40% full successes (healing of inflammation and improvement of function) and 30% satisfactory results (healing of inflammatory signs, without improvement of function). Failures amount to 17% and 13% of the patients cannot be thoroughly controlled. With regard to the failures, alternative treatment might be attempted with cyclosporin A, plasmapheresis or perhaps immunostimulation.

Alopecia↗

PubMed2002

Universal approach to pharmacokinetic monitoring of immunosuppressive agents in children.

Current data indicate that pharmacokinetic (PK) monitoring of cyclosporin microemulsion (CsA) should be performed using the 2-h concentration (C2), that tacrolimus (Tac) is commonly monitored using the trough level, and mycophenolate mofetil (MMF) should be monitored using the 1-h (C1), 2-h (C2) and 6-h (C6) concentrations. The three differing time-point requirements are cumbersome, and we aimed to develop universal guidelines for all three drugs using a large number of full PK profiles in children. One-hundred and twenty two stable pediatric patients, receiving either CsA (165 PK profiles, 69 patients, 24 with concomitant MMF) or Tac (122 PK profiles, 53 patients, 18 with MMF) were analyzed retrospectively. Pearson r for the CsA C2 was 0.90 [95% confidence interval(CI): 0.86-0.92], for Tac C2 r was 0.86 (95% CI: 0.80-0.90), and for MPA C2 r was 0.77 (95% CI: 0.68-0.83), respectively. For MPA, at least three time-points are required to accurately estimate the area under the concentration-time curve (AUC), and C1, C2 and C6 serve as best markers. Excellent AUC estimations could be obtained from a limited sampling strategy from C1, C2 and C6 or C0, C1, C2 and C4 with clinically acceptable errors for all three drugs. The AUC can be estimated with great precision by using an identical approach for all three drugs. Target AUCs for a given time-point after transplantation remain to be established.

Adolescent↗

PubMed2004

The effects of pretreatment with donor antigen and immunosuppressive agents on fully allogenic tracheal graft.

BACKGROUND: Obliterative bronchiolitis is a major clinical problem in cases involving a transplanted lung. We examined drug-induced tolerance to a fully allogenic tracheal graft in a murine heterotopic transplantation model. MATERIALS AND METHODS: Recipient mice (C57BL/6) were primed iv with 1 x 10(8) splenocytes of donor mice (BALB/c). Day 0 was the day of the splenocyte injection. Cyclophosphamide and Busulfan were injected intraperitoneally on day 2. On day 3, 1 x 10(7) donor bone marrow cells were intravenously injected. On day 28, a donor tracheal graft was implanted into a subcutaneous pocket. Grafts were harvested at 3-week intervals, and the degree of obstruction of the inner cavity, the condition of epithelium, and the viability of chondrocytes were examined. RESULTS: All of the isograft controls (BALB/c) and grafts implanted in the T cell-free recipients (BALB/c-nu) showed patent, lined epithelium and viable chondrocytes. All allografts tested showed total luminal occlusion by granulative tissue and inflammatory cells, and the epithelium was totally absent. Five of 11 drug-treated grafts were completely patent, although the epithelium was almost absent and the chondrocytes were substantially destroyed. However, when the chimerism was analyzed by flow cytometry analysis of the recipient T cells, approximately 90% of the donor cells were recognized. CONCLUSIONS: Even by this pre-treatment-induced chimerism, a transplanted allogenic trachea was not completely preserved. The present results suggest that a non-allogenic response might have contributed to the rejection.

Animals↗

PubMedDate not supplied

Is histology useful for the assessment of the efficacy of immunosuppressive agents in IBD and if so, how should it be applied ?

Crohn's disease and ulcerative colitis are two chronic relapsing inflammatory bowel diseases of unknown etiology. Both conditions are characterized by a considerable morbidity and have an impact upon the social and economic aspects of the patients life. At present, medical treatment is mainly aiming at the control of the inflammation. Drugs used for ulcerative colitis can induce microscopic healing of the mucosa. Similar results have been obtained recently with immunomodulatory drugs in Crohn's disease. The cost of these drugs is however high and the use of these drugs can be associated with side effects. Furthermore, many of the drugs need to be given for a long period. Therefore it is appropriate to assess the efficacy of the drugs before commercial use and even when used in routine practice. For both ulcerative colitis and Crohn's disease, clinical parameters combined in indices and endoscopy are commonly used together with some laboratory tests for the assessment of disease activity. In ulcerative colitis, histology has been used along with the other instruments for the measurement of disease activity because it was shown that the mucosal lesions could improve. More recently, histology has also been used for Crohn's disease. Routinely, disease activity when assessed with microscopy, should be divided into mild, moderate and severe. For drug trials and study purposes, more objective scoring systems should be used. Preferentially, a generally accepted score is used. This allows comparisons between different studies. Different scoring systems have been designed for ulcerative colitis and Crohn's disease. For the latter, multiple biopsies should be analysed. Most scoring systems still need validation.

Biopsy↗

PubMed2005

Safety of tacrolimus, an immunosuppressive agent, in the treatment of rheumatoid arthritis in elderly patients.

OBJECTIVE: To prospectively evaluate the safety of tacrolimus in active rheumatoid arthritis (RA) in elderly patients with insufficient response to disease-modifying antirheumatic drugs (DMARDs). METHODS: Fifty-seven patients aged > or =65 yr with RA for > or =6 months were enrolled in an open-label, non-controlled study. All DMARDs were discontinued and tacrolimus was administered orally once daily after the evening meal for 28 weeks. Tacrolimus, initiated at 1.5 mg/day, was increased to 3 mg/day after 6 weeks if no abnormal changes developed. Existing NSAID and oral corticosteroid (< or =7.5 mg/day prednisolone equivalent) therapy could be continued during the study. Safety was evaluated as clinical symptoms, abnormal changes in laboratory values and the development of infection. Treatment response was determined using the American College of Rheumatology (ACR) criteria for improvement. Whole blood concentrations of tacrolimus 12 h after administration were measured by high-performance liquid chromatography and tandem mass spectrometry. RESULTS: Clinical adverse events developed in 25 patients (46.3%). Abnormal changes in laboratory values occurred in 25 patients (46.3%). Ten patients (18.5%) developed infection. An ACR20 response was achieved by 50.0% of efficacy-evaluable patients and ACR20 success rates (the proportion of patients achieving ACR20 response and completing the study) was 46.3%. The ACR50 response rate was 18.5% of evaluable patients. Mean blood concentration of tacrolimus was 3.3 and 5.3 ng/ml in patients receiving 1.5 and 3.0 mg daily, respectively. No relationship between its concentration and adverse reactions was observed. CONCLUSION: In elderly patients with insufficient response to DMARD therapy, tacrolimus at 1.5-3.0 mg/day is safe and well-tolerated and provides clinical benefit.

Administration, Oral↗

PubMed2005

Effects of immunosuppressive agents on magnesium metabolism early after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The calcineurin inhibitors, cyclosporine A (CSA) and tacrolimus, cause hypomagnesemia by suppressing reabsorption of magnesium (Mg) from renal tubules. To assess whether the effect on Mg metabolism after allogeneic hematopoietic stem cell transplantation (HSCT) differs among calcineurin inhibitors, we prospectively evaluated the Mg metabolism in recipients of allogeneic HSCT who received CSA or tacrolimus METHODS: Patients who underwent allogeneic HSCT were enrolled. CSA and tacrolimus were given by continuous infusion starting from day -1. Serum Mg and the total amount of urinary Mg excretion were measured once before starting of CSA or tacrolimus, and once weekly after HSCT for 4 weeks. Mg was supplemented with magnesium l-aspartate by continuous infusion to maintain the serum Mg level >1.4 mEq/L. RESULTS: Thirty-six patients were evaluated (12 in the CSA group, 24 in the tacrolimus group). The serum Mg level began to decrease in both groups at the first week after HSCT, and the mean serum Mg levels were significantly lower in the tacrolimus group than in the CSA group from the first to the third week. The total amount of urinary Mg excretion and Mg supplementation began to increase in both groups at the second week after HSCT, and the amounts in the tacrolimus group were significantly higher than those in the CSA group. CONCLUSIONS: Although both calcineurin inhibitors increased urinary Mg excretion and caused hypomagnesemia shortly after HSCT, the effect was more significant with tacrolimus than with CSA. This observation may explain the higher incidence of renal impairment and encephalopathy in patients receiving tacrolimus.

Adult↗

PubMed1994

Tepoxalin, a novel immunosuppressive agent with a different mechanism of action from cyclosporin A.

Tepoxalin, a compound previously identified as a dual cyclooxygenase/lipoxygenase (CO/LO) inhibitor, is a potent inhibitor of T cell proliferation. Comparing the suppressive effects of tepoxalin and cyclosporin A (CsA) on OKT3-, PMA-, IL-2-, and PMA+ionomycin-induced T cell proliferations revealed marked differences in the mechanism of action between the two compounds. Whereas CsA was most effective in suppressing OKT3-stimulated proliferation, tepoxalin was more potent in inhibiting PMA-, PMA+ionomycin-, and IL-2-induced proliferation. Quantitative PCR (QPCR) assays used to detect cytokine messages showed that tepoxalin blocked IL-2 mRNA transcription in PMA- and PMA+ionomycin-, but not OKT3-stimulated T cells whereas CsA was most potent in inhibiting OKT3-induced IL-2 mRNA induction in these cells. Both tepoxalin and CsA did not inhibit the expression of IL-2R; however, only tepoxalin, but not CsA, inhibited the proliferation of IL-2-dependent blasts and the transcription of IFN-gamma, an IL-2-dependent target gene. Moreover, addition of exogenous IL-2 restored OKT3-induced proliferation to CsA- but not tepoxalin-treated cells. These data suggest that tepoxalin, but not CsA, suppressed T cell proliferation by inhibiting IL-2-induced signal transduction. Consistent with these findings, tepoxalin, unlike CsA, which was most potent when added at the initiation of OKT3 stimulation, was equally active, regardless of whether it was added at the beginning or 48 h after culture initiation. The difference in mechanism of action between tepoxalin and CsA was confirmed further by the synergistic suppressive effects on T cell proliferation upon co-administration of the two compounds.

Base Sequence↗

PubMed1993

Leflunomide, a novel immunosuppressive agent. The mechanism of inhibition of T cell proliferation.

Leflunomide is a novel immunomodulating drug that has recently been demonstrated to prevent acute rejection and reverse ongoing rejection of kidney and cardiac allografts in rats. In vitro studies here demonstrate that leflunomide suppresses proliferation of human PBL stimulated with (1) allogeneic PBL in a one-way MLR (50% inhibition with 50-25 microM); (2) anti-CD3 mABs plus PMA (50% inhibition with 70 microM leflunomide); and (3) anti-CD28 mABs plus PMA (50% inhibition with 65 microM leflunomide). In contrast, CsA only inhibited T cell proliferation stimulated by anti-CD3 plus PMA. Leflunomide partially inhibited IL-2 production of T cells stimulated with anti-CD3 plus PMA or anti-CD28 plus PMA, whereas CsA completely inhibited IL-2 production by T cells stimulated by the CD3 pathway and only partially inhibited IL-2 production by T cells stimulated by the CD28 pathway. Because comparable levels of IL-2 were produced by CD28-stimulated T cells treated with either CsA or leflunomide, but no inhibition of proliferation was observed in the CsA-treated cultures, we hypothesized that the lowering of IL-2 levels was not the mechanism by which leflunomide inhibited T cell proliferation. This hypothesis was supported by the observations that exogenous IL-2 failed to restore the T cell proliferation in the presence of leflunomide. Loss of T cell responsiveness to IL-2 in the presence of leflunomide was not due loss of expression of IL-2 receptors. Collectively, our data suggest that inhibition of T cell proliferation by leflunomide occurs via inhibition of responsiveness to IL-2.

Antigens, CD↗

PubMed1983

Studies on antinephritic effect of mizoribine (p-INN, Bredinin), a new immunosuppressive agent, and azathioprine (1) effect on the nephrotic type of anti-GBM nephritis in rats.

The present study was made to investigate the antinephritic effect of mizoribine in comparison to that of azathioprine by using the nephrotic type of anti-rat glomerular basement membrane rabbit serum (anti-GBM serum)-induced nephritis in rats. The nephrotic type nephritis was induced in rats by two i.v. injections of anti-GBM serum at a 10 day interval. Both drugs were given orally, daily from the 2nd day following the first injection of anti-GBM serum to the 21st day. Mizoribine in doses of 5 and 7.5 mg/kg/day significantly inhibited urinary protein excretion by 30-40% on the 22nd day. Mizoribine at both doses showed an inhibitory tendency on urinary alkaline phosphatase (ALP) excretion on the 9th and 16th days. On the 22nd day, this drug at a dose of 7.5 mg/kg/day inhibited plasma cholesterol (CL) content by 59.6% and wet weight of kidneys by approx. 50%, but no significant difference was seen between the drug-treated and control groups. When renal tissues on the 22nd day were observed under light microscopy, mizoribine at both doses remarkably prevented glomerular changes such as mesangial proliferation and thickening of capillary walls and significantly inhibited the index of glomerular lesions (IGL) by over 60%. On the other hand, azathioprine at a dose of 20 mg/kg/day was as effective as mizoribine at 5 mg/kg/day in inhibiting urinary protein and ALP excretions, plasma CL content and kidney weight. However, azathioprine showed little effect on the IGL. From these results, mizoribine at the dose level of 1/4 to 1/3 of azathioprine showed a more potent effect than azathioprine in this model. Therefore, mizoribine is also expected to have a beneficial effect on nephrotic type nephritis in clinical fields.

Animals↗

PubMed2000

Treatment with cytotoxic immunosuppression agents increases urinary excretion of JCV in patients with autoimmune disease.

Human JC virus is ubiquitous in human populations and is reactivated frequently in immunosuppressed patients. Fifty-one patients with autoimmune disease receiving immunomodulating therapy were evaluated to study the possible relationship between immunosuppression and JCV viruria. Patients were divided into cytotoxic and noncytotoxic treatment groups based on their prescription. The incidence of JCV viruria in the cytotoxic treatment group was significantly higher than that in the noncytotoxic group (67% vs. 28%; P < 0.05). Most patients with JCV viruria were receiving corticosteroid (P = 0.03 for any dose and P < 0.001 for higher-dose treatments) and cytotoxic agents (P = 0.02). Age, disease duration, and medication duration appeared not to be the precipitating factors of JCV viruria in this study. The results of clinical evaluation indicate that cytotoxic immunosuppression may play an important role in JC virus reactivation.

Adolescent↗