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Synergistic immunomodulatory effects of interferon‐β1b and the phosphodiesterase inhibitor pentoxifylline in patients with relapsing‐remitting multiple sclerosis
Author(s) -
Weber Frank,
Polak Thomas,
Günther Astrid,
Kubuschok Boris,
Janovskaja Julia,
Bitsch Andreas,
Poser Sigrid,
Rieckmann Peter
Publication year - 1998
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410440109
Subject(s) - pentoxifylline , multiple sclerosis , cytokine , interferon beta 1b , peripheral blood mononuclear cell , in vivo , interferon , medicine , tumor necrosis factor alpha , immunology , rolipram , myelin basic protein , downregulation and upregulation , interferon gamma , lymphotoxin , pharmacology , in vitro , myelin , phosphodiesterase , biology , enzyme , central nervous system , biochemistry , microbiology and biotechnology , interferon beta , gene
Subcutaneous application of interferon‐β1b (IFN‐β1b) 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‐β1b and the phosphodiesterase inhibitor pentoxifylline (PTX) on proliferation and the production of tumor necrosis factor‐α (TNF‐α), lymphotoxin (LT), and interferon‐γ (IFN‐γ). In an initial, open labeled prospective trial, the cytokine messenger RNA (mRNA) expression of blood mononuclear cells from MS patients, receiving either IFN‐β1b alone or in combination with oral PTX, was determined by semi‐quantitative reverse transcriptase polymerase chain reaction (RT‐PCR). Patients treated with IFN‐β1b alone reported more side effects during the first 3 months of treatment and had upregulated TNF‐α as well as IFN‐γ 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‐β1b with PTX is a promising approach to correct the disturbed cytokine balance in MS patients.