Protective Effects of Infliximab on Lung Injury Induced by Methotrexate

Introduction: Methotrexate (MTX) is used to treat cancers, several forms of arthritis and other rheumatic conditions, although MIX may cause pulmonary toxicity related to the production of free oxygen radicals, various cytokines. Infliximab (IB) with its potent effect on tumor necrosis factor-alpha (TNF-alpha) inhibition also inhibits the release of endothelin-1 (ET-1). We aimed to investigate whether IB reduces pulmonary damage induced by an overdose of MIX. Method: The rats were divided into 3 groups of 8 animals. The control group was given only saline. One dose of 20 mg/kg MIX intraperitoneal was administered in the MIX group. IB 7 mg/Kg was given to the MTX+ IB (MI) group. Three days after IB was administered, 20 mg/kg MIX was given. Five days after MTX was administered, all rats were sacrificed. Results: The TNF-alpha, ET-1, malondialdehyde (MDA), myeloperoxidase (MPO) and caspase-3 levels in MTX group were significantly higher than in control groups of TNF-alpha (P=.001), ET-1 (P=.001), MDA (P=.001), MPO (P=.001) and caspase-3 levels (P=.001) and MI groups of TNF-alpha (P =.009), ET-1 (P=.001), MDA (P=.047), MPO (P=.007) and caspase-3 levels (P=.003). The MI group had less histopathological damage in lung tissue than the MTX group. Conclusion: Overdose of MTX leads to cytokine release and the formation of reactive oxygen species in addition to increased ET-1 secretion release that causes lung damage. IB, as a potent proinflammatory agent, TNF-alpha blocker, can decrease ET-1 release and oxidative stress, it may show significant protective effects in lung tissue against damage caused by MTX overdose. (C) 2014 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved.