Synergistic immunomodulatory effects of interferon‐β1b and the phosphodiesterase inhibitor pentoxifylline in patients with relapsing‐remitting multiple sclerosis

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Abstract
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.

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