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Review
. 2023 Jul 31;12(15):5039.
doi: 10.3390/jcm12155039.

Reversing the Inflammatory Process-25 Years of Tumor Necrosis Factor-α Inhibitors

Katharina N Muth  1 , Juergen Rech  2   3 , Florian O Losch  1 , André Hoerning  3   4
Affiliations
Review

Reversing the Inflammatory Process-25 Years of Tumor Necrosis Factor-α Inhibitors

Katharina N Muth et al. J Clin Med. .

Abstract

Immune-mediated inflammatory diseases, such as rheumatoid arthritis, psoriatic arthritis, peripheral and/or axial spondyloarthritis, Crohn's disease, and ulcerative colitis, are characterized by molecular and cellular changes in the immune system. Due to the systemic nature of these diseases, organs such as the liver or cardiovascular system are often affected by the inflammatory process. Tumor necrosis factor-α inhibitor therapy reduces the activation of pro-inflammatory signaling cascades, mitigates the chronic inflammatory process by restoring cellular balance, and alleviates clinical consequences, such as pain and tissue damage.

Keywords: cytokines; immune-mediated inflammatory diseases; inflammation; liver; rheumatoid arthritis; tumor necrosis factor alpha-inhibitors.

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Conflict of interest statement

K.N.M. and F.O.L. are employees of Hexal AG. J.R. has received research grants from Sobi and Novartis and speaker’s fees, honoraria, and travel expenses from AbbVie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Novartis, Sanofi, Sobi, and UCB. A.H. has received research grants for clinical studies and speaker’s fees, honoraria, and travel expenses from AbbVie, Hexal AG, Novartis, Nutricia, Orphalan, Sanofi, and Shire/Takeda.

Figures

Figure 1
Figure 1
The cytokine TNF-α is a superordinate and crucial node within the hierarchical structure of cytokine networks underlying various chronic inflammatory diseases. Abbreviations: axSpA, axial spondyloarthritis; CD, Crohn’s disease; IL, interleukin; JIA, juvenile idiopathic arthritis; PsA, psoriatic arthritis; PsO, psoriasis; RA, rheumatoid arthritis; TNF, tumor necrosis factor; UC, ulcerative colitis.
Figure 2
Figure 2
Simplified presentation of the development and chronification of inflammatory processes by the impaired balance between pro- and anti-inflammatory cytokines, e.g., in rheumatoid arthritis. Abbreviations: GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; IL, interleukin; TGF, tumor necrosis growth factor; TH, T helper cell; TNF, tumor necrosis factor; Treg, regulatory T cell. The size of the cytokines depicted schematically represents their released amount.
Figure 3
Figure 3
Therapy with a TNF-α inhibitor restores the cytokine balance in chronic inflammatory diseases and, thus, also the cellular balance. Abbreviations: IFN, interferon; IL, interleukin; TGF, tumor necrosis growth factor; TH, T helper cell; TNF, tumor necrosis factor; Treg, regulatory T cell. The size of the cytokines depicted schematically represents their released amount.
See this image and copyright information in PMC

References

    1. McGonagle D., Stockwin L., Isaacs J., Emery P. An enthesitis based model for the pathogenesis of spondyloarthropathy. additive effects of microbial adjuvant and biomechanical factors at disease sites. J. Rheumatol. 2001;28:2155–2159. - PubMed
    1. Furman D., Campisi J., Verdin E., Carrera-Bastos P., Targ S., Franceschi C., Ferrucci L., Gilroy D.W., Fasano A., Miller G.W., et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 2019;25:1822–1832. doi: 10.1038/s41591-019-0675-0. - DOI - PMC - PubMed
    1. Gabay C., Kushner I. Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 1999;340:448–454. doi: 10.1056/NEJM199902113400607. - DOI - PubMed
    1. Germolec D.R., Shipkowski K.A., Frawley R.P., Evans E. Markers of inflammation. Methods Mol. Biol. 2018;1803:57–79. doi: 10.1007/978-1-4939-8549-4_5. - DOI - PubMed
    1. Stavropoulou E., Pircalabioru G.G., Bezirtzoglou E. The role of cytochromes P450 in infection. Front. Immunol. 2018;9:89. doi: 10.3389/fimmu.2018.00089. - DOI - PMC - PubMed

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