TY - JOUR
T1 - Giant cell arthritis (gca)-scid mice chimeras as a treatment model for human vasculitis
AU - Biask, A. J.
AU - Geisler, A.
AU - Martincz-Taboada, V.
AU - Goronzy, J.
AU - Weyand, C.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
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M3 - Article
AN - SCOPUS:33749444315
SN - 1708-8267
VL - 44
SP - 221a
JO - Journal of Investigative Medicine
JF - Journal of Investigative Medicine
IS - 3
ER -