ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1766

GM-CSF Is a Pro-Inflammatory Cytokine in Experimental Vasculitis of Medium and Large Arteries

Ryu Watanabe 1, Hui Zhang 2, Toshihisa Maeda 3, Mitsuhiro Akiyama 2, Rohan Gandhi 4, John Paolini 5, Gerald Berry 1 and Cornelia Weyand2, 1Stanford University, Stanford, 2Stanford University, Stanford, CA, 3Matsubara Mayflower Hospital, Kobe, Japan, 4Kiniska Pharmaceuticals, San Diego, 5Kiniska Pharmaceuticals, Lexington, MA

Meeting: 2019 ACR/ARP Annual Meeting

Keywords:

Session Information

Date: Monday, November 11, 2019

Title: 4M088: Cytokines & Cell Trafficking (1764–1769)

Session Type: ACR Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Giant Cell Arteritis (GCA) is a granulomatous vasculitis with tissue tropism for medium and large arteries. Macrophages are a key cellular component of the granulomatous infiltrates and contribute to the disease process through the production of cytokines, growth factors and tissue-injurious proteases. Lesional macrophages can fuse to form the typical giant cells, the namesakes of the disease. To which extent the number of macrophages in the vasculitis lesions affects the intensity of inflammation is unknown. We have tested whether granulocyte-macrophage colony-stimulating factor (GM-CSF), a soluble cytokine involved in the generation the survival and the activation of macrophages has a role in exacerbating vascular inflammation. In a preclinical animal model of vasculitis, we have injected recombinant GM-CSF (rGM-CSF) or blocked GM-CSF activity by treating with Mavrilimumab (KPL-301), a monoclonal antibody, which inhibits the GM-CSF receptor-α.

Methods: Vasculitis was induced in human artery mouse chimeras by engrafting medium-sized human arteries and adoptively transferring peripheral blood mononuclear cells from patients with GCA. One group of mice received 50 ug of recombinant GM-CSF. Another group of mice was treated with control IgG or anti-GM-CSF. Another group of mice was treated with control IgG or anti-GM-CSFRα antibody intraperitoneally over one week. Arteries were harvested and examined by Hematoxylin and eosin staining and tissues transcripts.

Results: Compared to treatment controls, recombinant GM-CSF intensified and KPL-301 reduced tissue inflammation in the arteries. The numbers of tissue-residing T cells doubled after rGM-CSF injection and was reduced by about 50% after treating with the blocking antibody. Changes in the density of inflammatory cells were accompanied by parallel changes in he tissue gene expression of IL-1β, IL-6 and IFN-γ. the tissue expressions of IL-17 and TNF-α transcripts were unaffected by either intervention.

Conclusion: We conclude that GM-CSF has a role as an inflammatory cytokine in medium vessel vasculitis. The density of inflammatory cells in the lesions appears to be GM-CSF dependent. the effect of GM-CSF seems selective, with IL-17 and TNF-α being independent of GM-CSF signaling in this model.

Disclosure: R. Watanabe, None; H. Zhang, None; T. Maeda, None; M. Akiyama, None; R. Gandhi, Kiniska Pharmaceuticals, 3; J. Paolini, Kiniska Pharmaceuticals, 3; G. Berry, None; C. Weyand, Kiniska Pharmaceuticals, 2.

To cite this abstract in AMA style:

Watanabe R, Zhang H, Maeda T, Akiyama M, Gandhi R, Paolini J, Berry G, Weyand C. GM-CSF Is a Pro-Inflammatory Cytokine in Experimental Vasculitis of Medium and Large Arteries [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/gm-csf-is-a-pro-inflammatory-cytokine-in-experimental-vasculitis-of-medium-and-large-arteries/. Accessed .

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/gm-csf-is-a-pro-inflammatory-cytokine-in-experimental-vasculitis-of-medium-and-large-arteries/