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At least 883 records · Page 49Linked to original sources
PubMed2006

Combined immunosuppressive agents or CD4 antibodies prolong survival of human neural stem cell grafts and improve disease outcomes in amyotrophic lateral sclerosis transgenic mice.

Amyotrophic lateral sclerosis (ALS) is a target for cell-replacement therapies, including therapies based on human neural stem cells (NSCs). These therapies must be first tested in the appropriate animal models, including transgenic rodents harboring superoxide dismutase (SOD1) mutations linked to familial ALS. However, these rodent subjects reject discordant xenografts. In the present investigation, we grafted NSCs from human embryonic spinal cord into the ventral lumbar cord of 2-month-old SOD1-G93A transgenic mice. Animals were immunosuppressed with FK506, FK506 plus rapamycin, FK506 plus rapamycin plus mycophenolate mofetil, or CD4 antibodies. With FK506 monotherapy, human NSC grafts were rejected within 1 week, whereas combinations of FK506 with one or two of the other agents or CD4 antibodies protected grafts into end-stage illness (i.e., more than 2 months after grafting). The combination of FK506 with rapamycin appeared to be optimal with respect to efficacy and simplicity of administration. Graft protection was achieved via the blockade of CD4- and CD8-cell infiltration and attenuation of the microglial phagocytic response from the host. Surviving NSCs differentiated extensively into neurons that began to establish networks with host nerve cells, including alpha-motor neurons. Immunosuppressed animals with live cells showed later onset and a slower progression of motor neuron disease and lived longer compared with immunosuppressed control animals with dead NSC grafts. Our findings indicate that combined immunosuppression promotes the survival of human NSCs grafted in the spinal cord of SOD1-G93A mice and, in doing so, allows the differentiation of NSCs into neurons and leads to the improvement of key parameters of motor neuron disease.

Amyotrophic Lateral Sclerosis↗
PubMed1978

[Immunosuppressive agents and Behçet's syndrome: critical analysis of results].

12 patients suffering from Behçet's disease have received immunosuppressive therapy. All patients have been given chlorambucil. In addition 5 patients who were threatened by an acute and permanent blindness from severe retinal vein involvement received antilymphocyte globulins. The follow-up ranges from 1 year up to 71/2 years with an average of 31/2 years. Complete recovery from ocular inflammation has been achieved in all patients. Visual acuity remained unchanged or improved in all patients but 1. Ocular recurrences occurred in 2 patients after decreasing the daily dose of chlorambucil and in 1 patient 2 years after the end of a 1-year treatment. The action of chlorambucil was not so constant upon systemic involvement of the disease than upon ocular inflammation. Nevertheless, 1 patient recovered from severe central nervous system involvement with hemiplegia. The review of the literature and comparison with our own experience leads to suggest that the discrepancy of the published results should be related to the variety of the immunosuppressive drugs which have been tried in Behçet's disease. Chlorambucil seems to be the most effective and the less toxic drug. But its action upon eye inflammation requires 2-3 months to take place. Therefore, in the most severe cases threatened by an acute and permanent blindness, the treatment should be started with antilymphocyte globulins.

Antilymphocyte Serum↗
PubMed1984

Cyclosporine: a new immunosuppressive agent for organ transplantation.

Cyclosporine, a cyclic endecapeptide of fungal origin, has recently been released for use in clinical transplantation. Trials in kidney, heart, liver and bone marrow recipients were encouraging: 1-year graft survival rates were 70% to 80% for kidney and heart recipients, and 60% to 65% for liver allograft recipients. Cyclosporine is also effective in treating bone marrow recipients with acute graft-versus-host disease. The drug selectively inhibits T-helper cell production of growth factors essential for B cell and cytotoxic T-cell differentiation and proliferation, while allowing expansion of suppressor T-cell populations. Drug absorption varies greatly, necessitating monitoring of drug level and individualization of therapy. Nephrotoxicity is the most frequent side effect of cyclosporine. An increased incidence of B-cell lymphomas seen when cyclosporine was used in conjunction with cytotoxic agents or anti-lymphocyte globulin has very rarely been observed when concomitant immunosuppression has been limited to low-dose corticosteroids. Lower initial doses of cyclosporine, followed by more rapid tapering may reduce the incidence of nephrotoxicity without compromising improved graft outcome.

Animals↗
PubMed1988

[Successful outcome of high-risk pregnancy within 1 year following kidney transplantation with cyclosporin as the immunosuppressive agent].

A 41-year-old female patient with analgesic nephropathy became pregnant 13 weeks after successful renal transplantation using cyclosporin as an immunosuppressant. Because of rhesus incompatibility of the mother this was thought to be a high risk pregnancy. In spite of the increased risk of CyA-induced nephrotoxicity in this early phase after transplantation, the patient showed the same physiological renal changes during pregnancy as healthy control patients: a 24% increase in creatinine clearance and an increase in protein excretion of only 41 mg/day. To maintain a CyA-blood concentration of 200-600 ng/ml throughout the pregnancy the CyA dose had to be increased from 380 to 550 mg daily or from 6.9 to 8.3 mg/kg/day (20%). This increase in CyA requirement may indicate additional metabolism of CyA by the fetal liver.

Adult↗
PubMed1992

Advantages of cyclosporine as sole immunosuppressive agent in children with transplanted kidneys.

A prospective study of intentional stopping of steroids 6 months after transplantation was done with 29 pediatric renal transplant recipients with a mean age of 10.4 +/- 3.4 years. Immunosuppression consisted of cyclosporine and methylprednisolone. We stopped giving MP to 24 children: to twenty after six months, four after 11-20 months. "Crude graft survival" was 97% during a mean follow-up of 36.7 +/- 15 months. The rejection rate was 48% during the first 6 months and 29% in the period after stopping MP. At present, 20/24 children (83%) have remained on CsA alone (18 patients) or CsA and azathioprine (2 patients) during a mean follow-up of 30 +/- 17 months. CsA nephrotoxicity occurred in 20.6% of patients, gum hypertrophy in 45%, hypertrichosis in 24%, and neurological symptoms in two patients (6.8%). Linear growth significantly improved after stopping MP: mean catch-up growth for prepuberal children 1.38 height standard deviation score (HSDS) and for pubertal children 1.6 HSDS. Bone age did not increase more rapidly than chronologic age. Weight/height index (W/HI) also improved. There was also a significant reduction in the use of antihypertensive drugs. Calculated glomerular filtration rate was decreased, though not significantly, after stopping MP. Thus, when graft survival is good, stopping corticosteroids corrects the major handicap of children with irreversible uremia--the poor linear growth--and improves the W/HI and control of arterial pressure. Longer follow-up periods are necessary to exclude significant worsening of renal function and an increased incidence of chronic rejection after stopping the steroid.

Adolescent↗
PubMed1988

Spleen lymphocyte populations and expression of activation markers in rats treated with the potent new immunosuppressive agent FK-506.

Rats were immunized systemically with sheep red blood cells (SRBC) and treated with either FK-506 (1 mg/kg/day) or cyclosporin A (CsA) (25 mg/kg/day) for 7 days. Profound (greater than 90%) suppression of the production of splenic IgM-secreting plasma cells and circulating antibody levels was observed in animals receiving either drug. Immunosuppression was accompanied by significant increases in the incidence and absolute numbers of OX8+ (T-cytotoxic/suppressor) lymphocytes in the spleen, and there were corresponding reductions in the W3/25+:OX8 (CD4+:CD8+) ratio. The magnitude of these changes was not affected by drug combination. There were no significant alterations in B cells with either agent, whilst a small but significant increase in the incidence of macrophages was observed in all drug-treated groups. Neither FK-506 nor CsA affected IL-2 receptor (OX39) or MHC class II (OX6) antigen expression. This study demonstrates the remarkable immunosuppressive potency of FK-506 and its underlying capacity, like CsA, to affect regulatory T-lymphocyte subsets in vivo.

Animals↗
PubMed1991

Pneumothorax in a patient with Wegener's granulomatosis during treatment with immunosuppressive agents.

We present the case of a 16-year-old woman with Wegener's granulomatosis, who developed a pneumothorax while receiving treatment with cyclophosphamide and glucocorticoids. The lung was re-expanded by tube drainage, and the patient recovered completely while the immunosuppressive treatment was continued in combination with sulphamethoxazole-trimethoprim. A possible role for this antimicrobial drug in the treatment of Wegener's granulomatosis is briefly discussed.

Adolescent↗
PubMed1971

Immunosuppressive agents in intracellular infection: besnoitiosis in hamsters.

When tested for their activity in suppressing the acquisition of immunity during acute Besnoitia infection of hamsters, antilymphocyte serum (ALS), aminopterin, cyclophosphamide, cortisol, and whole-body irradiation were the most active agents and effectively blocked the development of immunity during 4 to 12 days of immunization. Actinomycin D and chlorambucil were moderately active, and nitrogen mustard, 6-mercaptopurine, and vinblastine exhibited slight immunosuppressive activity. Established immunity was especially labile to cortisol and cortisone administration with generalized Besnoitia relapse occurring consistently in all hamsters; this occurred infrequently during cyclophosphamide treatment. Focal relapse was seen in chronically irradiated and ALS-treated hamsters, but the location of the lesions differed. Irradiated hamsters had lesions in the lungs and brain, whereas ALS-treated hamsters showed splenic relapse. Acquisition of immunity was more sensitive to suppression than established immunity and did not necessarily parallel antibody development and vice versa, emphasizing the importance of cellular over humoral factors in immunity to this intracellular parasite.

Journal Article↗
PubMed1988

Comparison of cyclophosphamide, cytarabine, and etoposide as immunosuppressive agents before allogeneic bone marrow transplantation.

Etoposide and cytarabine have been shown to exert high antileukemic activity and are currently under study as preparatory agents before allogeneic bone marrow transplantation. However, data concerning their engraftment-promoting potency are scarce. Therefore, we tested these agents in LEW rats receiving a myeloablative dose of busulfan followed by transfer of F1 (CAP X LEW) marrow, which is unable to induce a graft-v-host reaction (GVHR). Since busulfan by itself has only minor immunosuppressive potency, graft rejection ensues unless etoposide, cytarabine, or cyclophosphamide provide additional immunosuppression to facilitate durable engraftment. Before allogeneic bone marrow transplantation in humans, 120 mg/kg of cyclophosphamide, 60 mg/kg of etoposide, or 900 mg/kg of cytarabine are the standard doses given in conjunction with total body irradiation. Seventy-five percent of these doses administered in addition to busulfan resulted in rejection rates of 75% for cytarabine and 58% for etoposide, respectively, whereas no rejections were observed with cyclophosphamide. These data indicate that etoposide and cytarabine are inferior to cyclophosphamide in their rejection-preventing potential. Using either of these agents as substitutes for cyclophosphamide before allogeneic bone marrow transplantation may increase the risk of graft rejection in HLA-mismatched bone marrow transplantation and, in case of HLA identity, if T-depleted marrow is administered.

Animals↗
PubMed1982

Cyclosporin a as sole immunosuppressive agent in recipients of kidney allografts from cadaver donors. Preliminary results of a European multicentre trial.

In a multicentre trial conducted in eight European centres, 232 recipients of cadaveric renal allografts were randomly allocated to receive either cyclosporin A (CyA, 117 patients) or azathioprine and steroids (control, 115 patients) for immunosuppression. After a follow-up period of up to 11 months, graft survival probability estimates are 73% in the CyA group and 53% in the control group. Two deaths have occurred in the CyA group and seven in the control group. 82% of the CyA group with functioning grafts are receiving CyA alone, 17% have been changed to azathioprine and steroids, and 1 patient is receiving prednisolone in addition to CyA; 27% have never received steroids. At 6 months post-transplant, renal function is similar in patients receiving CyA and in those receiving azathioprine and steroids. These preliminary results suggest that CyA is more effective than conventional immunosuppression. CyA therapy avoids the necessity of long-term steroid therapy.

Azathioprine↗
PubMed1980

Immunosuppressive agents in corticosteroid-refractory childhood dermatomyositis.

Five patients with childhood dermatomyositis, followed for 18 to 96 months, improved when treated with a combination of corticosteroids and methotrexate (one patient) or corticosteroids and cyclophosphamide (four patients) after having become refractory to corticosteroid therapy alone. Complications of vascular involvement in childhood dermatomyositis or from immunosuppressive therapy were observed in most of these patients. Disease components involving skin, muscle, or systemic vessels sometimes varied independently in regard to disease activity or therapeutic responsiveness. In two patients with stable or improving muscle function, cerebrovascular complications occurred. Monitoring of disease activity was best accomplished by clinical evaluation; serum muscle enzymes usually failed to rise prior to or during periods of clinical worsening.

Child↗