Minocycline-Induced Lupus

Schlienger, Raymond G.; Bircher, Andreas J.; Meier, Christoph

doi:10.1159/000018387

Cited by 105 publications

(49 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, minocycline is a potential trigger of drug-induced lupus, and recent studies demonstrate a clear association between increased NFAT1 activity in T cells and systemic lupus erythematosus (55)(56)(57)(58). Paradoxically, in cases of minocyclineinduced lupus, higher doses might prove therapeutic through increased suppression of NFAT1.…”

Section: Discussionmentioning

confidence: 99%

Minocycline Suppresses Activation of Nuclear Factor of Activated T Cells 1 (NFAT1) in Human CD4+ T Cells

Szeto¹,

Pomerantz

Graham

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Minocycline is a tetracycline family antibiotic that has antiinflammatory and immunomodulatory properties. These properties have shown promise in the treatment of conditions such as rheumatoid arthritis, Huntington disease, and multiple sclerosis. As lymphocyte activation is involved in the pathogenesis of many of these diseases, T cells are postulated to be a primary target in minocycline therapy. Previous studies have demonstrated attenuation of CD4 ؉ T cell activation by minocycline, but a specific mechanism has not been elucidated. In this study, we investigated the effect of minocycline on the activity of three key transcription factors regulating CD4 ؉ T cell activation:NF-B, AP-1 (activator protein 1), and NFAT (nuclear factor of activated T) cells. Our data demonstrate that minocycline selectively impairs NFAT-mediated transcriptional activation, a result of increased phosphorylation and reduced nuclear translocation of the isoform NFAT1. Minocycline increased the activity of the NFAT kinase GSK3 and decreased intracellular Ca 2؉ flux, both of which facilitate NFAT1 phosphorylation. These findings provide a novel mechanism for minocycline induced suppression of CD4 ؉ T cell activation and may better inform the application of minocycline as an immunomodulatory agent.The tetracycline family of antibiotics is known to have multiple biological activities distinct from their antimicrobial function. Over the past two decades, the tetracycline derivative minocycline has demonstrated neuroprotective and immunomodulatory effects in animal models of diseases, including multiple sclerosis and Parkinson and Huntington diseases (1-3). Interest in the mechanism of its neuroprotective abilities has driven extensive research on minocycline-induced effects on inflammatory signaling in monocyte lineage cells, particularly the brain-resident microglia (4 -6). Modulation of T cell activation and function has also been proposed as one of the major mechanisms of action of minocycline.T cell activation contributes to disease pathogenesis by creating an inflammatory environment that leads to cellular damage and death as well as decreased immune function. Minocycline has been found to be therapeutic in multiple diseases whose pathogenesis is significantly T cell driven by modulating cellular activation and function. In rheumatoid arthritis patients, minocycline significantly improved clinical symptoms and increased the frequency of remissions leading to its usage as a disease modifying anti-rheumatic drug (7-9). Studies using CD4 ϩ T cell clones derived from the synovium of an rheumatoid arthritis patient showed that minocycline decreased activation-induced proliferation and inflammatory cytokine production (10). Minocycline has also shown therapeutic effects on T cells in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Minocycline treatment of rodents with experimental autoimmune encephalomyelitis attenuated the severity of encephalitis, decreased T cell transmigration in vitro, and reduced CD4...

show abstract

Section: Discussionmentioning

confidence: 99%

Minocycline Suppresses Activation of Nuclear Factor of Activated T Cells 1 (NFAT1) in Human CD4+ T Cells

Szeto¹,

Pomerantz

Graham

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Anti-dsDNA antibodies have been observed in patients with TNF-a inhibitor DIL (81) but are rare in procainamide and hydralazine DIL (68). The serologic profile of minocycline DIL is also different from other DIL with the occurrence of positive ANA, anti-dsDNA antibodies, and p-ANCA (82). Complement levels are variably reduced in DIL, and hypocomplementemia is seen more commonly with quinidine and TNF-a inhibitors (67,69).…”

Section: Dil Epidemiology Clinical Presentation and Pathogenesismentioning

confidence: 99%

Drug-Induced Glomerular Disease

Hogan

Markowitz²,

Radhakrishnan

2015

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Drug-induced autoimmune disease was initially described decades ago, with reports of vasculitis and a lupus-like syndrome in patients taking hydralazine, procainamide, and sulfadiazine. Over the years, multiple other agents have been linked to immune-mediated glomerular disease, often with associated autoantibody formation. Certain clinical and laboratory features may distinguish these entities from their idiopathic counterparts, and making this distinction is important in the diagnosis and management of these patients. Here, drug-induced, ANCA-associated vasculitis, drug-induced lupus, and drug-associated membranous nephropathy are reviewed.

show abstract

“…43,48 Because minocycline therapy has the potential for harmful adverse reactions, many authors have confirmed the need for physicians to perform pharmacovigilance, or monitoring of the safety of minocycline drug therapy regimens, to detect serious adverse effects. 4,6,15,16,19,20,25,26,31,34,38,42,[44][45][46]49,50 According to the Guide to Physical Therapist Practice, the initial examination "is a comprehensive screening and specific testing process leading to diagnostic classification, or, as appropriate, to a referral to another practitioner." 2 The inclusion of a comprehensive pharmacovigilance component in the patient examination process augments the ability of the physical therapist to identify when a referral to another practitioner is warranted.…”

Section: Drug-induced Lupusmentioning

confidence: 99%