Lipid metabolism in autoimmune rheumatic disease: implications for modern and conventional therapies
George Robinson, Ines Pineda-Torra, Coziana Ciurtin, Elizabeth C. Jury
George Robinson, Ines Pineda-Torra, Coziana Ciurtin, Elizabeth C. Jury
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Lipid metabolism in autoimmune rheumatic disease: implications for modern and conventional therapies

Abstract

Suppressing inflammation has been the primary focus of therapies in autoimmune rheumatic diseases (AIRDs), including rheumatoid arthritis and systemic lupus erythematosus. However, conventional therapies with low target specificity can have effects on cell metabolism that are less predictable. A key example is lipid metabolism; current therapies can improve or exacerbate dyslipidemia. Many conventional drugs also require in vivo metabolism for their conversion into therapeutically beneficial products; however, drug metabolism often involves the additional formation of toxic by-products, and rates of drug metabolism can be heterogeneous between patients. New therapeutic technologies and research have highlighted alternative metabolic pathways that can be more specifically targeted to reduce inflammation but also to prevent undesirable off-target metabolic consequences of conventional antiinflammatory therapies. This Review highlights the role of lipid metabolism in inflammation and in the mechanisms of action of AIRD therapeutics. Opportunities for cotherapies targeting lipid metabolism that could reduce immunometabolic complications and potential increased cardiovascular disease risk in patients with AIRDs are discussed.

Authors

George Robinson, Ines Pineda-Torra, Coziana Ciurtin, Elizabeth C. Jury

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Figure 2

Summary of the mechanisms of action of current therapies used in AIRDs.

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Summary of the mechanisms of action of current therapies used in AIRDs. ...
Schematic representation summarizing the key mechanistic pathways affected by both traditional and modern therapies used to treat AIRDs, including disease-modifying antirheumatic drugs (DMARDs), target synthetic DMARDs (tsDMARDs), nonsteroidal antiinflammatory drugs (NSAIDs), steroids, and biologics. The majority of these therapeutics result in the modification of immune functions and metabolic pathways through alterations in gene transcription. These pathways provide insight into opportunities for cotherapies to prevent off-target immunometabolic effects. AA, arachidonic acid; Aza, azathioprine; CP, cyclophosphamide; GF, growth factor; GR, glucocorticoid receptor; HCQ, hydroxychloroquine; NF-κB, nuclear factor NF-κB (p50/p52/RelA/RelB/); IκB, inhibitor of κB; MAP2/3K, mitogen-activated protein 2-kinase or 3-kinase; MMF, mycophenolate mofetil; MTX, methotrexate; NFAT, nuclear factor of activated T cells; PG, prostaglandin; R, receptor; RXR, retinoid X receptor; SASP, sulfasalazine; SYK, spleen-associated tyrosine kinase; TCR, T cell receptor.