Kim, Youn-Jung Song, Mee Ryu, Jae-Chun 2024-01-20T21:04:57Z 2024-01-20T21:04:57Z 2021-09-03 2009-07 1474-0338 https://pubs.kist.re.kr/handle/201004/132373 Background: Methotrexate (MTX) has been widely used for the treatment of inflammatory diseases and rheumatoid arthritis, as well as a variety of tumors. However, MTX-induced pulmonary toxicity is a serious and unpredictable side effect of the therapy, which includes allergic, cytotoxic or immunologic reactions, and is a major clinical problem. Objective: To summarize the mechanisms of action involved in MTX-induced pulmonary toxicity. Methods: We reviewed the literature describing MTX-induced adverse pulmonary effects and the mechanisms of action underlying MTX-induced pulmonary toxicity. Conclusion: The mechanisms underlying MTX toxicity are complex. The clinical effects may be attributable to both the anti-inflammatory and immunosuppressive effects of MTX The mechanisms causing the side effects of MTX include mutation of the genotype, inhibition of transport, MTX-polyglutamates and P-glycoprotein binding with MTX The p38 MAPK-signaling pathway is especially associated with a pulmonary inflammatory response. These mechanisms can be applied to optimize drug treatment. English TAYLOR & FRANCIS LTD ACTIVATED PROTEIN-KINASE LOW-DOSE METHOTREXATE INTERSTITIAL LUNG-DISEASES BLOOD MONONUCLEAR-CELLS RHEUMATOID-ARTHRITIS GENE-EXPRESSION ALVEOLAR MACROPHAGES INDUCED PNEUMONITIS EPITHELIAL-CELLS HYPERSENSITIVITY PNEUMONITIS Mechanisms underlying methotrexate-induced pulmonary toxicity Article 10.1517/14740330903066734 1 EXPERT OPINION ON DRUG SAFETY, v.8, no.4, pp.451 - 458 EXPERT OPINION ON DRUG SAFETY 8 4 451 458 scie scopus 000267864700005 2-s2.0-67650511052 Pharmacology & Pharmacy Pharmacology & Pharmacy Review ACTIVATED PROTEIN-KINASE LOW-DOSE METHOTREXATE INTERSTITIAL LUNG-DISEASES BLOOD MONONUCLEAR-CELLS RHEUMATOID-ARTHRITIS GENE-EXPRESSION ALVEOLAR MACROPHAGES INDUCED PNEUMONITIS EPITHELIAL-CELLS HYPERSENSITIVITY PNEUMONITIS mechanism methotrexate p38 MAPK pulmonary toxicity