SYNERGISTIC IMMUNOMODULATORY EFFECTS OF INTERFERON-BETA-1B AND THE PHOSPHODIESTERASE INHIBITOR PENTOXIFYLLINE IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE-SCLEROSIS

Subcutaneous application of interferon-beta 1b (IFN-beta 1b) is an est ablished therapy for patients with relapsing-remitting multiple sclero sis (RRMS), but early side effects are still a major concern. In vitro studies with myelin basic protein (MBP)-specific T-cell lines reveale d a synergistic suppressive effect of IFN-beta 1b and the phosphodiest erase inhibitor pentoxifylline (PTX) on proliferation and the producti on of tumor necrosis factor-alpha (TNF-alpha), lymphotoxin (LT), and i nterferon-gamma (IFN-gamma). In an initial, open labeled prospective t rial, the cytokine messenger RNA (mRNA) expression of blood mononuclea r cells from MS patients, receiving either IFN-beta 1b alone or in com bination with oral PTX, was determined by semi-quantitative reverse tr anscriptase polymerase chain reaction (RT-PCR). Patients treated with IFN-beta 1b 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-beta 1b with MX is a promising approa ch to correct the disturbed cytokine balance in MS patients.