Long-term effect of IFNbeta1b treatment on the spontaneous and induced expression of IL-10 and TGFbeta1 in MS patients.

Interferon-beta (IFNbeta) is an effective treatment that lessens the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (RRMS). The mechanism of action of IFNbeta1b may be by upregulating antiinflammatory cytokines levels. We studied the effect of IFNbeta1b treatment on the in vivo gene expression and protein synthesis of two immunosuppressive cytokines, IL-10 and TGFbeta1, and its persistence with chronic therapy.

Induction of functional CD154 (CD40 ligand) in neonatal T cells by cAMP-elevating agents.

A deficiency of neonatal T lymphocytes to express CD154 antigen in response to ionomycin and phorbol 12-myrsistate 13-acetate (PMA) stimulation or after CD3 cross-linking has been described. In the present report we describe that CD45RA+ newborn cells are able to synthesize and express CD154 at similar or even higher levels than adult cells in response to ionomycin and cAMP-elevating agents which trigger the protein kinase A (PKA) -mediated metabolic pathway. Peak CD154 protein concentrations in newborn cells were found between 4 and 8 hr after stimulation with ionomycin and dibutyryl cAMP.

Interferon beta-1b treatment modulates TNFalpha and IFNgamma spontaneous gene expression in MS.

Background: Interferon beta (IFNbeta) lessens the overall frequency of acute attacks in patients with the relapsing-remitting form of multiple sclerosis (RRMS). IFNbeta may act by decreasing the synthesis of inflammatory cytokines.

Objectives: To determine whether IFNbeta-1b treatment had an initial and sustained effect on the in vivo synthesis and secretion of tumor necrosis factor alpha (TNFalpha) and IFNgamma.

Glucocorticoids inhibit IL-4 and mitogen-induced IL-4R alpha chain expression by different posttranscriptional mechanisms.

Background: A high level of expression of IL-4Ralpha chain on the surface of lymphocytes has been described in certain allergic and inflammatory autoimmune diseases. Progression of these diseases are usually controlled by steroid treatment. One mechanism by which these drugs exert their antiinflammatory and immunosuppressive effects is by widely repressing or enhancing the production of cytokines and their receptors.

Glucocorticoids increase IL-10 expression in multiple sclerosis patients with acute relapse.

High doses of glucocorticoids (GCs) are widely employed to treat acute attacks in relapsing-remitting multiple sclerosis (MS) patients. Their beneficial effects are partially due to their capacity to regulate the cytokine network. In the present work, we have examined the effect of GCs on the production of the immunosuppressor cytokine IL-10.

Requirement of a second signal via protein kinase C or protein kinase A for maximal expression of CD40 ligand. Involvement of transcriptional and posttranscriptional mechanisms.

High levels of CD40 ligand (CD40L) protein expression are induced on native T cells by increasing the intracellular Ca2+ concentration. In the present study we have shown that ionomycin induces CD40L gene transcription leading to mRNA accumulation which translates to high levels of protein expression. Conversely, agents which increase the intracellular levels of cyclic AMP (cAMP), such as prostaglandin E2 (PGE2) or dibutyryl cyclic AMP (dbcAMP), were unable to induce CD40L expression on T lymphocytes.

Upregulated expression of IL-4 receptors and increased levels of IL-4 in rheumatoid arthritis patients.

The level of IL-4R expression on peripheral lymphocyte subsets from rheumatoid arthritis (RA) patients and controls was studied by flow cytometric analysis of the binding of phycoerythrin-labelled IL-4 (PE-IL-4). In normal lymphocytes, IL-4R is mainly expressed on CD19+ cells, although it was also seen, at lower levels, on CD3+, CD4+ and CD8+ cells. In RA patients, a significantly increased spontaneous expression of IL-4R was observed, compared with controls, in the CD3+, CD4+ and CD19+ cell subsets.

Soluble, but not immobilized, anti-IgM antibody inhibits post-activation events leading to T-cell-dependent B-cell differentiation.

The potential for surface immunoglobulin-binding ligands to modify B-cell differentiation responses induced by activated T cells has been investigated. Activated T cells in human splenic mononuclear cells cultured on anti-CD3-coated plates induced B cells to produce large amounts of IgM and IgG. In this experimental system, cross-linking of B-cell antigen receptors by soluble, bivalent monoclonal or polyclonal anti-IgM antibodies completely inhibited IgM production, and greatly diminished IgG production, in a dose-dependent manner.