Immunotherapy of Autoimmune Diseases with Nonantibiotic Properties of Tetracyclines

Overview

Journal Immune Netw

Specialty Allergy & Immunology

Date 2021 Jan 11

PMID 33425432

Citations 10

Authors

Chan-Su Park

Sang-Hyun Kim

Chong-Kil Lee

Affiliations

Soon will be listed here.

Abstract

Tetracyclines, which have long been used as broad-spectrum antibiotics, also exhibit a variety of nonantibiotic activities including anti-inflammatory and immunomodulatory properties. Tetracyclines bind to the 30S ribosome of the bacteria and inhibit protein synthesis. Unlike antimicrobial activity, the primary molecular target for the nonantibiotic activity of tetracycline remains to be clarified. Nonetheless, the therapeutic efficacies of tetracyclines, particularly minocycline and doxycycline, have been demonstrated in various animal models of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, and asthma. In this study, we summarized the anti-inflammatory and immunomodulatory activities of tetracyclines, focusing on the mechanisms underlying these activities. In addition, we highlighted the on-going or completed clinical trials with reported outcomes.

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References

Snijders G, van den Ende C, van Riel P, van den Hoogen F, den Broeder A . The effects of doxycycline on reducing symptoms in knee osteoarthritis: results from a triple-blinded randomised controlled trial. Ann Rheum Dis. 2011; 70(7):1191-6. DOI: 10.1136/ard.2010.147967. View

Xu X, Abdalla T, Bratcher P, Jackson P, Sabbatini G, Wells J . Doxycycline improves clinical outcomes during cystic fibrosis exacerbations. Eur Respir J. 2017; 49(4). DOI: 10.1183/13993003.01102-2016. View

Smith Jr G, Mickler E, Hasty K, Brandt K . Specificity of inhibition of matrix metalloproteinase activity by doxycycline: relationship to structure of the enzyme. Arthritis Rheum. 1999; 42(6):1140-6. DOI: 10.1002/1529-0131(199906)42:6<1140::AID-ANR10>3.0.CO;2-7. View

Mei X, Xu H, Xie C, Ren J, Zhou Y, Zhang H . Post-injury administration of minocycline: an effective treatment for nerve-injury induced neuropathic pain. Neurosci Res. 2011; 70(3):305-12. DOI: 10.1016/j.neures.2011.03.012. View

Baugh M, Perry M, Hollander A, Davies D, Cross S, Lobo A . Matrix metalloproteinase levels are elevated in inflammatory bowel disease. Gastroenterology. 1999; 117(4):814-22. DOI: 10.1016/s0016-5085(99)70339-2. View

Bernardino A, Kaushal D, Philipp M . The antibiotics doxycycline and minocycline inhibit the inflammatory responses to the Lyme disease spirochete Borrelia burgdorferi. J Infect Dis. 2009; 199(9):1379-88. PMC: 3697124. DOI: 10.1086/597807. View

Frankwich K, Tibble C, Torres-Gonzalez M, Bonner M, Lefkowitz R, Tyndall M . Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetes. J Inflamm (Lond). 2012; 9(1):35. PMC: 3507843. DOI: 10.1186/1476-9255-9-35. View

Niimi N, Kohyama K, Matsumoto Y . Minocycline suppresses experimental autoimmune encephalomyelitis by increasing tissue inhibitors of metalloproteinases. Neuropathology. 2013; 33(6):612-20. DOI: 10.1111/neup.12039. View

Patel A, Khande H, Periasamy H, Mokale S . Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model. Inflammation. 2020; 43(3):1035-1043. PMC: 7224120. DOI: 10.1007/s10753-020-01188-y. View

10.

Minagar A, Alexander J, Schwendimann R, Kelley R, Gonzalez-Toledo E, Jimenez J . Combination therapy with interferon beta-1a and doxycycline in multiple sclerosis: an open-label trial. Arch Neurol. 2007; 65(2):199-204. DOI: 10.1001/archneurol.2007.41. View

11.

Castro J, Vado-Solis I, Perez-Osorio C, Fredeking T . Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever. Clin Dev Immunol. 2011; 2011:370872. PMC: 3065216. DOI: 10.1155/2011/370872. View

12.

Yulug B, Hanoglu L, Ozansoy M, Isik D, Kilic U, Kilic E . Therapeutic role of rifampicin in Alzheimer's disease. Psychiatry Clin Neurosci. 2018; 72(3):152-159. DOI: 10.1111/pcn.12637. View

13.

Loeb M, Molloy D, Smieja M, Standish T, Goldsmith C, Mahony J . A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease. J Am Geriatr Soc. 2004; 52(3):381-7. DOI: 10.1111/j.1532-5415.2004.52109.x. View

14.

Kloppenburg M, Verweij C, Miltenburg A, Verhoeven A, Daha M, Dijkmans B . The influence of tetracyclines on T cell activation. Clin Exp Immunol. 1995; 102(3):635-41. PMC: 1553388. DOI: 10.1111/j.1365-2249.1995.tb03864.x. View

15.

Kim N, Park C, Im S, Kim J, Lee J, Park Y . Minocycline promotes the generation of dendritic cells with regulatory properties. Oncotarget. 2016; 7(33):52818-52831. PMC: 5288151. DOI: 10.18632/oncotarget.10810. View

16.

Metz L, Li D, Traboulsee A, Duquette P, Eliasziw M, Cerchiaro G . Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis. N Engl J Med. 2017; 376(22):2122-2133. DOI: 10.1056/NEJMoa1608889. View

17.

Attur M, Patel R, Patel P, Abramson S, Amin A . Tetracycline up-regulates COX-2 expression and prostaglandin E2 production independent of its effect on nitric oxide. J Immunol. 1999; 162(6):3160-7. View

18.

Giuliani F, Hader W, Yong V . Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction. J Leukoc Biol. 2005; 78(1):135-43. DOI: 10.1189/jlb.0804477. View

19.

Ingham E, Turnbull L, Kearney J . The effects of minocycline and tetracycline on the mitotic response of human peripheral blood-lymphocytes. J Antimicrob Chemother. 1991; 27(5):607-17. DOI: 10.1093/jac/27.5.607. View

20.

Henehan M, Montuno M, De Benedetto A . Doxycycline as an anti-inflammatory agent: updates in dermatology. J Eur Acad Dermatol Venereol. 2017; 31(11):1800-1808. DOI: 10.1111/jdv.14345. View