ABSTRACT
The effect of interferon (IFN)beta-1a and IFNbeta-1b on human myelin basic protein-reactive T-cell lines was investigated. Both drugs inhibited proliferation and production of lymphotoxin (LT), whereas the production of interleukin-4 was not altered and interleukin-10 was induced. Comparing equal numbers of units IFNbeta-1a and -1b showed almost identical results. These in vitro data indicate that the immunomodulatory capacity of both interferons with respect to T cells paralleled their antiviral effect.
Subject(s)
Interferon-beta/immunology , Myelin Basic Protein/drug effects , T-Lymphocytes/immunology , Analysis of Variance , Cell Line/drug effects , Cell Line/immunology , Cytokines/biosynthesis , Humans , Interferon beta-1a , Interferon beta-1b , Interferon-beta/pharmacology , Lymphocyte Activation/immunology , Models, Immunological , T-Lymphocytes/drug effectsABSTRACT
Subcutaneous application of interferon-beta1b (IFN-beta1b) is an established therapy for patients with relapsing-remitting multiple sclerosis (RRMS), but early side effects are still a major concern. In vitro studies with myelin basic protein (MBP)-specific T-cell lines revealed a synergistic suppressive effect of IFN-beta1b and the phosphodiesterase inhibitor pentoxifylline (PTX) on proliferation and the production of tumor necrosis factor-alpha (TNF-alpha), lymphotoxin (LT), and interferon-gamma (IFN-gamma). In an initial, open labeled prospective trial, the cytokine messenger RNA (mRNA) expression of blood mononuclear cells from MS patients, receiving either IFN-beta1b alone or in combination with oral PTX, was determined by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Patients treated with IFN-beta1b alone reported more side effects during the first 3 months of treatment and had upregulated TNF-alpha as well as IFN-gamma mRNA expression during the first month, which was not detected in patients receiving both drugs. A synergistic effect of both drugs was observed on the upregulation of interleukin (IL)-10 mRNA, which was accompanied by an increase in IL-10 serum levels. Both in vitro and in vivo data suggest that co-treatment of IFN-beta1b with PTX is a promising approach to correct the disturbed cytokine balance in MS patients.
