Giant cell arthritis (gca)-scid mice chimeras as a treatment model for human vasculitis

A. J. Biask, A. Geisler, V. Martincz-Taboada, J. Goronzy, C. Weyand

Research output: Contribution to journalArticlepeer-review

Abstract

GCA is an inflammatory vasculitis affecting an elderly population and occasionally leading to blindness. Although treated successfully with corticosteroids, little is known about their mechanism of action on the inflammatory vascular lesion. We have established an animal model by subcutaneously implanting temporal artery biopsy specimens from patients with biopsy proven GCA into SC1D mice. Four weeks after transplantation, specimens were retrieved and examined histochemically. Overall, histomorphology after xenotransplantation was preserved and all relevant populations of inflammatory cells, including CD4+, CD8+ and CD68+ cells, were identified. Semiquamification of cytokine mRNA of macrophage and T cell origin by PCR did not demonstrate any significant reduction as a consequence of transplantation supporting the concept of a functional integrity of the inflammatory infiltrate. We took advantage of this animal model to characterize the effects of steroid treatment in vivo. Short-term treatment (0.4 mg/kg dexamethasone i.p. once daily for 7 days) resulted in a 40-50% reduction of cell proliferation and in the number of infiltrating T cells compared to sham-treated mice. However, the production of macrophage and lymphocyte derived cytokines was unchanged on steroid treatment. After 28 days of treatment, the copy numbers of cytokine mRNA were significantly reduced, monokines and lymphokines were both affected. Our data show that steroids do not have an immediate effect on T cell-macrophage interaction and subsequent cytokine production in the tissue. Longterm treatment leads to an attenuation of the inflammatory response.

Original languageEnglish (US)
Pages (from-to)221a
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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