Cytogenetic effects of treatment with methotrexate and infliximab in rheumatoid arthritis patients

Abstract

Interaction between two anti-rheumatic drugs, infliximab (monoclonal antibody against tumour necrosis factor α; TNFα) and methotrexate (MTX; disease-modifying anti-rheumatic drug), was analysed in peripheral blood lymphocyte cultures using cytogenetic tests. Genotoxicity of low MTX doses was established in peripheral blood lymphocyte cultures in vitro and in peripheral blood lymphocytes from rheumatoid arthritis (RA) patients treated with MTX for short or long periods. In cell culture, blockade of TNFα before cell exposure to MTX significantly decreased the number of baseline and MTX-induced sister chromatid exchanges, showing a possible protective effect of infliximab. However, a significant impairment of cell proliferative abilities was observed in lymphocytes from RA patients after treatment with infliximab and MTX. Our study suggests that some anti-rheumatic drugs can impair the genetic stability and proliferation of immune cells in RA patients. These effects can be responsible for the increased risk of infectious diseases and cancer observed among arthritis patients. Keywords: rheumatoid arthritis, infliximab, methotrexate, sister chromatid exchanges, proliferative abilities