Session Title: Systemic Lupus Erythematosus – Animal Models - Poster II
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Dysregulation of innate and adaptive immune responses contributes to the pathogenesis of systemic lupus erythematosus (SLE) and its associated premature vascular damage. To date, no drug targets both systemic inflammatory disease and the cardiovascular complications of SLE. Tofacitinib is a Janus kinase (JAK) inhibitor that blocks signaling downstream of multiple cytokines implicated in lupus pathogenesis. While clinical trials have shown that tofacitinib exhibits significant clinical efficacy in various autoimmune diseases, its role in SLE and on its associated vascular pathology remains to be characterized.
Methods: MRL/lprlupus-prone mice received tofacitinib or vehicle by gavage for 6 weeks (therapeutic arm) or 8 weeks (preventive arm). Nephritis, skin inflammation, serum autoantibody levels and cytokines, mononuclear cell phenotype and gene expression, neutrophil extracellular trap (NET) release, endothelium-dependent vasorelaxation and endothelial differentiation were compared in treated and untreated mice.
Results: Treatment with tofacitinib led to significant improvement in measures of disease activity including nephritis, skin inflammation, and autoantibody production. In addition, tofacitinib treatment reduced serum levels of pro-inflammatory cytokines and interferon responses in splenocytes and kidney tissue. Tofacitinib also modulated NET formation and significantly increased endothelium-dependent vasorelaxation and endothelial differentiation. The drug was effective as both preventive and therapeutic strategies
Conclusion: Tofacitinib modulates the innate and adaptive immune responses, ameliorates murine lupus and improves vascular function. These results indicate that JAK inhibitors have the potential to be beneficial in SLE and its associated vascular damage.
To cite this abstract in AMA style:Furumoto Y, Smith CK, Blanco LP, Tsai WL, Zhao W, Hoffmann V, Thacker S, Sciumè G, Nuñez L, Remaley A, O'Shea JJ, Kaplan M, Gadina MG. The Janus Kinase Inhibitor Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/the-janus-kinase-inhibitor-tofacitinib-ameliorates-murine-lupus-and-its-associated-vascular-dysfunction/. Accessed February 18, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-janus-kinase-inhibitor-tofacitinib-ameliorates-murine-lupus-and-its-associated-vascular-dysfunction/