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At least 19 recordsLinked to original sources
PubMed1982

Differences among immunosuppressive agents.

Immunosuppressive agents have diverse (although often multiple) sites of action in the cell sequences that are involved in immune responses. New routes to selectivity are apparent at both the cellular and the biochemical level. Meanwhile, clinical work is finding new uses and more selective employment of the currently available agents.

Adenosine Deaminase↗
PubMed1996

Isolated glomeruli and cultured mesangial cells as in vitro models to study immunosuppressive agents.

Immunosuppressive agents, such as cyclosporin A (CsA), by their vasoconstrictive properties, induce in vivo in patients and rodents a dramatic fall in renal hemodynamics. The aim of this study is to review the ability of some physiological and/or pharmacological agents which are supposed to be involved in the renal physiopathology of CsA to prevent the contraction induced by CsA in two in vitro glomerular models. Isolated glomeruli are obtained by a sieving method from male Sprague-Dawley rat superficial cortex. Mesangial cells from these isolated glomeruli are cultured in RPM1 1640 medium with 20% FCS in 5% CO2 atmosphere. The area of isolated glomeruli and cultured mesangial cells is assessed by an image analyzer with a video camera. Each glomerulus and cell is its own control and is photographed before incubation with any drug (T0) and then during incubation at 5, 10, 20, and 30 min. Incubations are performed during 30 min with 10(-6) mol/L CsA either with a 10 min pretreatment with the vasoactive agent or without pretreatment. CsA alone induces a time- and dose-dependent decrease in glomerular structure area (-4.7% at 10 min, -10.3% at 20 min, and -12.0% at 30 min for isolated glomeruli); Cremophore excipient or control solute does not induce any significant decrease in surface area. CsA with 10(-6) mol/L verapamil pretreatment induces only a slight decrease: -1.5% at 10 min, -3.0% at 20 min, and -4.8% at 30 min. Calcium blockers nifedipine and felodipine produce similar results. Likewise, with 10(-8) mol/L prostacyclin analog (iloprost), only a slight area decrease in mesangial cells is noted: -1.3% at 5 min, -1.8% at 10 min, and -3.3% at 20 min; with 10(-6) mol/L TXA2 synthesis inhibitor (CGS 12970) the results are -2.0% at 10 min, -3.6% at 20 min, and -4.3% at 30 min. Finally, a similar protective effect can be noted with 10(-5) mol/L theophylline: -0.4; -1.5 and -1.9% at 10, 20, and 30 min. In conclusion, CsA-induced contraction in two in vitro glomerular models can be partially or even totally prevented by pretreatment with various pharmacological agents.

Animals↗
PubMed1989

[Metastasizing squamous cell carcinoma in patients with psoriasis treated with immunosuppressive agents].

Immunosuppressive agents are imployed increasingly frequently in treatment of nonfatal disorders. We report two cases of metastasizing squamous cell carcinoma after treatment for psoriasis with methotrexate. Additional cases must be reported, but we consider that: 1) methotrexate medication, when possible, should be withdrawn when a localized squamous cell carcinoma is diagnosed and 2) when this diagnosis is confirmed the patient should be referred for radical treatment.

Aged↗
PubMed1989

Different inhibitory actions of immunomodulating agents and immunosuppressive agents on bone resorption of mouse calvaria.

In this study, we have investigated the in vitro effects of the immunomodulators lobenzarit and traxanox and a newly synthesized immunosuppressant, mizoribine, as well as cyclosporin A, on bone resorption using neonatal mouse calvariae labelled with 45Ca. As stimulators of bone resorption, bovine parathyroid hormone (PTH), lipopolysaccharide (LPS), interleukin 1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) were used. Lobenzarit, traxanox, mizoribine and cyclosporin A inhibited or tended to inhibit bone resorption stimulated by PTH, LPS, IL-1 beta or TNF-alpha in a dose-dependent manner. Basal bone resorption was inhibited by immunosuppressant cyclosporin A or mizoribine, while immunomodulators lobenzarit and traxanox failed to inhibit basal bone resorption. Removal of lobenzarit from the culture medium resulted in the recovery of bone resorptive activity. These results suggest that the inhibitory effect of immunomodulators on bone resorption is reversible and nonselective. Also, it raises the possibility that immunomodulators and immunosuppressants may affect bone resorption by different mechanisms.

Adjuvants, Immunologic↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. II. Immunogenicity of antigen-immunosuppressive-agent conjugates].

The maintenance of specific immunogenicity of carrier proteins is a necessary condition for the successful use of antigen-immunosuppressive agent-conjugates (AIC) for an antigen specific suppression of the immune response. The experimental results indicate that, in spite of the binding of 6-mercaptopurine (6-MP) and toluyl (T) to bovine gamma globulin (BGG) and human serum albumin (HSA), the carrier specific immunogenicity is not significantly altered. The intradermal application of 6-MP-BGG and T-BGG emulsified with complete Freund's adjuvant in guinea pigs results, in all cases, in a well detectable anti BGG hemagglutination and precipitation titer. This kind of immunization leads also to a formation of anti 6-mercaptopurine and anti new antigen determinants (NAD's) antibodies.

Animals↗
PubMed1988

Neurologic complications of immunosuppressive agents.

The immunosuppressive agents that are an integral part of organ transplantation serve to protect grafts from rejection as well as to prevent or treat GVHD. They include CsA, corticosteroids, OKT3 monoclonal antibody, HDARA-C, azathioprine, and ATG. Of these, all but azathioprine and ATG have direct neurologic complications that are due to the drugs themselves and not just excessive immune suppression. With increasing success in solid organ and bone marrow transplantation and increasing patient survival, one can expect to see more patients who suffer neurologic toxicity.

Adrenal Cortex Hormones↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. I. Tentative hypothesis for the induction of antigen-specific suppression by antigen-immunosuppressive-agent conjugates].

The most important mechanisms for the specific depression of immune reactions--immuno-tolerance, enhancement, transfer of antibodies, drug induced tolerance, immunological suicide, application of antibody-toxin-complexes--are discussed with regard to their possible application in the clinical practice. A tentative hypothesis for induction of antigen specific suppression is proposed, basing on the use of antigen-immunosuppressive agent-conjugates (AIC). Antigen binding lymphocytes are supposed to bind the AIC and to pick them up through endocytosis. After breakdown of the AIC in the lymphoid cells the free immunosuppressive agent can become effective causing damage to the specific cell clones.

Animals↗
PubMed1992

The pharmacokinetics and pharmacodynamics of immunosuppressive agents.

Designing immunosuppressive regimens for the pediatric transplant patient is challenging because one must balance the need to provide adequate immunosuppression without interfering with normal growth processes or causing long-term adverse consequences. To optimize immunosuppressive therapy and minimize toxicity, it is necessary for the nurse to be knowledgeable of the pharmacokinetic and pharmacodynamic characteristics of the various agents. It is also important to understand which drugs interact with immunosuppressive agents and how to manage these interactions.

Adrenal Cortex Hormones↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. IV. Studies on the specific suppression of humoral immune response in guinea pigs by antigen-immunosuppressive-agent conjugates].

Bovine gamma globulin (BGG) antigens were modified by the binding of 6-mercaptopurine and toluyl residues, and their influence on the humoral immune response in guinea pigs was investigated. The antigen-immunosuppressive agent-conjugates (AIC) were different, depending on the method used for their preparation and the number of coupled residues per one molecule of BGG. Conjugates denoted as MPI-n-BGG were prepared by special chemical binding of corresponding thioisocyanates. MPII-n-BGG were synthetized by acetylation, and MPIII-n-BGG conjugates, by reductive alkylation. Pretreatment of guinea pigs with MPIII-19-BGG, MPII-16-BGG resulted in a stimulatory effect on the subsequent humoral immune response induced by BGG application. A significant suppressive influence was detectable if the animals had been pretreated with MPII-6-BGG and MPI-26-BGG. MPI-13-BGG and MPI-36-BGG had no effect on the later induced anti-BGG antibody formation. The immune response against a second antigen (human serum albumin) was not influenced by this kind of pretreatment of the animals. Therefore it seems justified to conclude that both stimulatory and suppressive effects seen here were antigen specific and that both the method for chemical modification and the number of coupled 6-MP residues are very important for their effectivity.

Agglutination↗
PubMed1991

RS-61443--a new, potent immunosuppressive agent.

The immunosuppressive activity of RS-61443, a semisynthetic derivative of mycophenolic acid, was examined in 33 canine renal allografts. Initial studies established that triple therapy consisting of 20 mg/kg RS-61443 in combination with 5 mg/kg cyclosporine and 0.1 mg/kg methylprednisolone was the optimal combination to prevent graft rejection. The median survival time was 8.1 +/- 1.2 days in dogs without treatment (n = 5), 8.5 +/- 1.7 days in the treatment control group (CsA 5 mg/kg, MP 0.1 mg/kg; n = 6), 36.0 +/- 9.6 days with RS-61443 monotherapy (40 mg/kg; n = 6); and 122.4 +/- 38.75 days with triple therapy (n = 16). Graft prolongation was statistically significant when compared with controls (P less than 0.05 and 0.002, respectively). Six recipients in the triple therapy group survived over 150 days without major adverse effects. Long-term administration of RS-61443 (20 mg/kg/day) did not cause nephrotoxicity, hematotoxicity, or hepatotoxicity, with the exception of a slight elevation of the alkaline phosphatase levels. Gastrointestinal symptoms including gastritis, diarrhea, and anorexia were common, especially under 40 mg/kg RS-61443 monotherapy, and appeared to be dose-related. Despite its immunosuppressive activity, an increased susceptibility to bacterial or viral infections was not observed. Histological studies of the kidney grafts revealed slight interstitial cell infiltration without vascular or glomerular damage.

Animals↗
PubMed1977

Niridazole as an immunosuppressive agent.

The immunosuppressive properties of niridazole, an antihelminthic drug, have been investigated in rats. When given orally at a dosage of 50 mg/kg it extended the median survival of cardiac allografts from 7 to 20 days. The immunosuppressive effect was not increased by giving either azathioprine or prednisolone concurrently, but when all three drugs were combined the immunosuppression was profound, and only 2 of 8 grafts were rejected. Drug combinations incorporating niridazole at a lower dosage or for a shorter period were less effective, and azathioprine and prednisolone on their own or together prolonged graft survival only marginally in this model.

Animals↗
PubMed1985

Immunological profile of DL111-IT, a new immunosuppressant agent.

The immunosuppressive properties of the non-hormonal contragestional agent 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole (DL111-IT) were evaluated on different immunological functions. The compound displayed significant immunosuppressive activity on both humoral and cellular immunity when administered during the inductive phase of the immune response. In experimental models autoimmunity and skin transplantation, DL111-IT was able to reduce the production of auto-antibodies and prolong skin graft survival. The compound, even at doses much higher than those effective inhibiting immune responses, did not influence the survival time of some haematological tumors in mice. This suggest that DL111-IT does not act by a general cytotoxic mechanism.

Animals↗
PubMed1991

Preclinical evaluation of a new potent immunosuppressive agent, rapamycin.

Since individual immunosuppressive agents display pleiotropic arrays of nonimmunologic toxic complications when used at therapeutic concentrations, synergistic drug combinations proffer an attractive strategy. RAPA is a good candidate for this enterprise, because of its unique action to inhibit lymphokine signal transduction. Initial in vivo and in vitro studies using the rigorous pharmacologic tool, the median effect analysis, document a synergistic relation between RAPA and CsA in rodent and canine models. These preclinical findings compel careful Phase I trials, in order to assess the safety and synergistic efficacy of RAPA in combination drug regimens with other immunosuppressive agents.

Animals↗