Immunosuppressive activity of an isoxazolo[5,4-e]triazepine--compound RM33. I. Effects on the humoral and cellular immune response in mice.
Journal Title: Pharmacological Reports - Year 2005, Vol 57, Issue 2
Abstract
The aim of this investigation was to evaluate immunotropic properties of a new isoxazolotriazepine (compound RM33) in mice. We found that RM33 significantly inhibited induction of the humoral immune response to sheep red blood cells (SRBC), given 2 h prior to immunization. The development of the cellular immune response (delayed type hypersensitivity--DTH) to SRBC and to ovalbumin (OVA) was also suppressed, as well as the effector phase of the DTH to OVA. The compound was also effective when administered per os. The suppressive effects of RM33 on the immune response were comparable to those of cyclosporine A(CsA). We also showed that RM33 inhibited DTH to OVA if admixed with the sensitizing dose of an antigen and complete Freund's adjuvant (cFa) suggesting that the compound may affect initial events of antigen presentation. Such a hypothesis was supported by finding that RM33 significantly inhibited foot pad edema elicited by administration of cFa. The effects of RM33 on the activities of cytokines relevant to development and control of the immune response and inflammation such as: tumor necrosis factor alpha (TNF-alpha), interleukin 6 and 10 (IL-6 and IL-10) were also studied. The compound markedly (by 63%) inhibited lipopolysaccharide (LPS)-induced TNF-alpha serum level whereas IL-6 activity was lowered to a lesser extent (by 17%). The inducible IL-10 level in the splenocyte cultures was not affected at all. In summary, the presented results revealed immunosuppressive properties of RM33, which could be associated with its selective interference with co-stimulatory signals provided by adjuvant at initiation of the immune response.
Authors and Affiliations
Stanisław Ryng, Michał Zimecki, Marcin Mączyński, Grzegorz Chodaczek, Maja Kocięba
Keywords
Related Articles
- EP ID EP144291
- DOI -
- Views 89
- Downloads 0
Enhanced oxidative stress in hypertrophic cardiomyopathy.
Elevated plasma levels of inflammation and endothelial dysfunction markers have been reported in patients with hypertrophic cardiomyopathy (HCM). The aim of the current study was to determine whether HCM is associated wi...
Combined treatment with imipramine and metyrapone induces hippocampal and cortical brain-derived neurotrophic factor gene expression in rats.
The problem of drug-resistant depression indicates a strong need for alternative antidepressant therapies. Recently it was shown that joint administration of imipramine (IMI) and metyrapone (MET), an inhibitor of glucoco...
Synthesis and cytotoxic activity of G3 PAMAM-NH(2) dendrimer-modified digoxin and proscillaridin A conjugates in breast cancer cells.
The objective of this study was to determine the cytotoxicity, antiproliferative activity, and apoptosis induction activity of two modified glycosides - digoxin and proscillaridin A - conjugated to a generation 3 polyami...
Effects of GABAB receptor agonists on cocaine hyperlocomotor and sensitizing effects in rats.
The present study was designed to find out whether pharmacological activation of GABA(B) receptors played a role in cocaine sensitization. To this end, male Wistar rats were injected with baclofen or 3-aminopropyl(methyl...
Mangiferin ameliorates 6-hydroxydopamine-induced cytotoxicity and oxidative stress in ketamine model of schizophrenia.
Background: Accumulating evidence indicates that mangiferin (MGF), a natural xanthone, by virtue of its antioxidant and antiinflammatory properties is neuroprotective. Here we sought to verify the cytoprotective role of...