The mechanism of action of recombinant interferon beta 1b (rIFN beta 1b/IFN beta-1b), the approved therapy for multiple sclerosis (MS), is still unclear. Here we present evidence that part of the therapeutic effects of rIFN beta 1b in MS might result from the induction of the secretion of interleukin (IL)-10, a cytokine previously designated cytokine synthesis inhibitory factor (CSIF). We observed that rIFN beta 1b stimulated significant IL-10 secretion by monocytes from MS patients after brief incubation (18 h), whereas rIFN gamma, an inducer of MS exacerbations, was unable to stimulate IL-10 production in similar conditions. To determine the role of IL-10 as CSIF in the disease, we have also investigated its effects on TNF alpha and IL-6 secretion by peripheral blood mononuclear cells from MS patients. Recombinant human IL-10 significantly inhibited tumor necrosis factor alpha and IL-6 secretion induced by rIFN gamma, lipopolysaccharide (LPS), and rIFN gamma + LPS in MS patients and in control subjects. The induction of IL-10 secretion by rIFN beta 1b and the IL-10 inhibitory activity on pro-inflammatory cytokine secretion induced by rIFN gamma in MS make this cytokine a potential candidate to treat the disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/0165-5728(95)00070-i | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Production of recombinant cytokines and polyclonal antibodies for analysis of cellular immune response in golden Syrian hamster.
Mol Biol Rep
September 2024
Laboratório de Vacinologia, Núcleo de Biotecnologia, Centro de Desenvolvimento Tecnológico, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Background: The development of therapies and vaccines for various diseases often necessitates the analysis of cellular immunity. However, unlike other rodents, the limited availability of reagents for Syrian hamsters restricts immunological analysis, particularly in the determination of serum effector molecules such as cytokines. In this study, we aim to produce and characterize the cytokines IFN-γ, TGF-β, IL-6, IL-10, and TNF-α from Syrian hamsters in recombinant form and to generate polyclonal antibodies against them in rats.
View Article and Find Full Text PDFRequirement of scavenger receptors for activation of the IRF-3/IFN-β/STAT-1 pathway in TLR4-mediated production of NO by LPS-activated macrophages.
Nitric Oxide
May 2023
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil. Electronic address:
Production of nitric oxide (NO) by LPS-activated macrophages is due to a complex cellular signaling initiated by TLR4 that leads to the transcription of IFN-β, which activates IRF-1 and STAT-1, as well as to the activation of NF-κB, required for iNOS transcription. High concentrations of LPS can also be uptaken by scavenger receptors (SRs), which, in concert with TLR4, leads to inflammatory responses. The mechanisms by which TLR4 and SRs interact, and the pathways activated by this interaction in macrophages are not elucidated.
View Article and Find Full Text PDFRecombinant Interferon-β in the Treatment of Polycythemia Vera and Related Neoplasms: Rationales and Perspectives.
Cancers (Basel)
November 2022
Department of Hematology, University Hospital Dubrava, 10000 Zagreb, Croatia.
About 30 years ago, the first clinical trials of the safety and efficacy of recombinant interferon-α2 (rIFN-α2) were performed. Since then, several single-arm studies have shown rIFN-α2 to be a highly potent anticancer agent against several cancer types. Unfortunately, however, a high toxicity profile in early studies with rIFN-α2 -among other reasons likely due to the high dosages being used-disqualified rIFN-α2, which was accordingly replaced with competitive drugs that might at first glance look more attractive to clinicians.
View Article and Find Full Text PDFType I Interferons Are Involved in the Intracellular Growth Control of by Mediating NOD2-Induced Production of Nitric Oxide in Macrophages.
Front Immunol
December 2021
Laboratory Animal Medicine, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, South Korea.
(MAB) is one of the rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) causing various diseases including pulmonary disorder. Although it has been known that type I interferons (IFNs) contribute to host defense against bacterial infections, the role of type I IFNs against MAB infection is still unclear. In the present study, we show that rIFN-β treatment reduced the intracellular growth of MAB in macrophages.
View Article and Find Full Text PDFSTING Agonist Mitigates Experimental Autoimmune Encephalomyelitis by Stimulating Type I IFN-Dependent and -Independent Immune-Regulatory Pathways.
J Immunol
May 2021
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC;
The cGAS-cyclic GMP-AMP (cGAMP)-stimulator of IFN genes (STING) pathway induces a powerful type I IFN (IFN-I) response and is a prime candidate for augmenting immunity in cancer immunotherapy and vaccines. IFN-I also has immune-regulatory functions manifested in several autoimmune diseases and is a first-line therapy for relapsing-remitting multiple sclerosis. However, it is only moderately effective and can induce adverse effects and neutralizing Abs in recipients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!