title: Metabolic profiling of human CD4+ cells following treatment with methotrexate and anti-TNF-α infliximab.
abstract: The autoimmune process in rheumatoid arthritis depends on activation of immune cells, which utilize intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. CD4+ T cells comprise a large proportion of the inflammatory cells that invade the synovial tissue and may therefore be a cell type of pathogenic importance. Both methotrexate and infliximab are effective in the treatment of inflammatory arthritis; however, the biological effects triggered by these treatments and the biochemical mechanisms underlining the cell response are still not fully understood. Thus, in this study the global metabolic changes associated with methotrexate or infliximab treatment of isolated human CD4+ T cells were examined using gas chromatography/mass spectrometry or liquid chromatography/mass spectrometry. In total 148 metabolites involved in selective pathways were found to be significantly altered. Overall, the changes observed are likely to reflect the effort of CD4+ cells to increase the production of cellular reducing power to offset the cellular stress exerted by treatment. Importantly, analysis of the global metabolic changes associated with MTX or infliximab treatment of isolated human CD4+ T cells suggested that the toxicity associated with these agents is minimal when used at clinically relevant concentrations.
authors: Rheumatology, Allergology and Clinical Immunology; Department of Internal Medicine; University of Rome Tor Vergata; Rome, Italy.
authors: Maria Sole
authors: MS
authors: Chimenti
authors: Paola
authors: P
authors: Tucci
authors: Eleonora
authors: E
authors: Candi
authors: Roberto
authors: R
authors: Perricone
authors: Gerry
authors: G
authors: Melino
authors: Anne E
authors: AE
authors: Willis
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D000069285:Infliximab; D013058:Mass Spectrometry; D055442:Metabolome / Q000187:drug effects*; D008727:Methotrexate / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D000964:Antimetabolites, Antineoplastic; D014409:Tumor Necrosis Factor-alpha; D006003:Glycogen; D000069285:Infliximab; D008727:Methotrexate
keywords: T cells; apoptosis; autoimmunity disease; rheumatoid arthritis
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