Article Text

PDF
AB0041 Large vessel vasculitis induced by candida albican water-soluble-fraction (CAWS) in the C57BL/6J mouse model is associated with overexpression of IL-6, TNF-α, and IL-10 with modest change in SOCS-1
  1. JM Springer1,
  2. M Zhang2,
  3. D Smith1,
  4. N Miura3,
  5. N Ohno3,
  6. O Tawfik4,
  7. M Maz1,
  8. K Dileepan1
  1. 1Allergy, Immunology and Rheumatology
  2. 2Department of Orthopedics, Kansas University Medical Center, Kansas City, United States
  3. 3Department of Pharmacy and Life Sciences, Tokyo University, Hachioji, Japan
  4. 4Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Kansas City, United States

Abstract

Background We have previously demonstrated that mast cell degranulation acutely downregulates lipopolysaccharide induced aortic expression and serum levels of IL-6 in vivo. This is accompanied by aortic upregulation of suppressor of cytokine signaling-1 (SOCS-1) gene expression1. This effect is not seen in histamine H1 receptor-knockout mice suggesting that mast cell-derived histamine is a key mediator involved in IL-6 homoeostasis2. Mice injected with Candida albican water-soluble-fraction (CAWS) have been shown to develop coronary and aortic vasculitis3. Our long-term objective is to determine the pathogenic mechanism of large vessel vasculitis (LVV).

Objectives The aim of this pilot study was to replicate and develop a working mouse model to determine the regulatory role of mast cells in LVV.

Methods Eight to ten weeks-old male C57Bl6/J mice were randomly distributed into two groups [CAWS, N=8; and Control, N=8] and were injected i.p. daily for 5 days with either CAWS in normal saline (2 mg/day/mouse) or normal saline alone (controls). All mice were sacrificed 30 days after the 5th injection. We examined serum levels of IL-6 and TNF-α, as well as aortic tissue expressions of IL-6, TNF-a, IL-10 and SOCS-1 mRNA. Heart and aortic sections were evaluated for inflammation and mast cells after staining with H & E and toluidine blue, respectively.

Results Treatment of mice with CAWS for 5-consecutive days led to overexpression of IL-6, TNF-a and IL-10 genes in the aortic tissue with modest upregulation of SOCS-1. At the root of the aorta, all animals in the CAWS group had intense inflammatory infiltrates composed of mixed acute and chronic inflammatory cells. There is also evidence of vasculitis in the coronary arteries. In contrast, none of the control mice had any evidence of aortic inflammation or vasculitis. Serum IL-6 concentrations were below detectable levels in both controls and CAWS-treated mice whereas TNF-a levels were elevated in 3 out of 8 mice in the CAWS group. There were no signs or increased presence of intact or degranulating mast cells in the area of inflammation.

Conclusions These results suggest that CAWS-induced LVV involves acute and chronic inflammatory response and vascular tissue expression of both pro- and anti-inflammatory cytokines and SOC-1. Detailed kinetic studies are warranted to determine the optimum windows of peak inflammatory response and the expression of these genes to understand the pathobiology of CAWS-induced LVV.

References

  1. Springer J, Raveendan V, Smith D, et al. [abstract] Ann Rheum Dis 2014;73:112–113.

  2. Raveendran V, Springer J, Smith D, et al. [abstract]. Arthritis Rheumatol 2015;67(suppl 10).

  3. Miura N, Shingo Y, Adachi Y, et al. Immunopharmacol Immunotoxicol 2004;26(4):527–43.

References

Acknowledgements Supported by Basic Science Development Award from Department of Medicine at the University of Kansas.

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.