Immunomodulation of murine experimental SLE-like disease by interferon-γ

被引:15
作者
Amital, H
Levi, Y
Blank, M
Barak, V
Langevirz, P
Afek, A
Nicoletti, F
Kopolovic, J
Gilburd, B
Meroni, PL
Shoenfeld, K
Shoenfeld, Y [1 ]
机构
[1] Tel Aviv Univ, Sackler Fac Med, Sheba Med Ctr, Dept Med B, IL-52621 Tel Hashomer, Israel
[2] Tel Aviv Univ, Sackler Fac Med, Sheba Med Ctr, Autoimmune Dis Res Unit, IL-52621 Tel Hashomer, Israel
[3] Hebrew Univ Jerusalem, Lab Tumor Immunol, Jerusalem, Israel
[4] Hadassah Med Sch, Jerusalem, Israel
[5] Tel Aviv Univ, Sackler Fac Med, Sheba Med Ctr, Rheumatol Unit, IL-69978 Tel Aviv, Israel
[6] Tel Aviv Univ, Sackler Fac Med, Sheba Med Ctr, Dept Med F, IL-69978 Tel Aviv, Israel
[7] Tel Aviv Univ, Sackler Fac Med, Sheba Med Ctr, Inst Pathol, IL-69978 Tel Aviv, Israel
[8] Dept Med Pathol & Metab Dis, Catania, Italy
[9] Univ Milan, IRCCS Policlin, Inst Internal Med Infect Dis & Immunopathol, Milan, Italy
关键词
systemic lupus erythematosus; IFN-gamma; Th1; cells; Th2; cytokines;
D O I
10.1191/096120398678920406
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The objective of this study was to assess the impact of murine recombinant IFN-gamma and anti-IFN-gamma monoclonal antibody on the BALB/c mice experimental model of lupus. BALB/c female mice were immunized with a human anti-DNA antibody that carries the 16/6 idiotype. These mice were divided into several therapeutic groups according to different treatment strategies; injection with mouse recombinant IFN-gamma, anti-IFN-gamma mAb, phosphate-buffered saline (PBS), irrelevant mouse IgG and control groups that were neither treated nor immunized with the human anti-DNA antibody. The administration of IFN-gamma intensified the degree of clinical, histological and serological parameters in this model of BALB/c murine lupus. This immunomanipulation decreased the mice longevity. All the laboratory parameters reflected acceleration of the disease in the IFN-gamma treated group as an elevated sedimentation rate, decreased white blood cell count and the development of massive proteinuria. One month after the boost injection, all the mice that were immunized with the anti-DNA antibody, developed high titers of autoantibodies; however, following an additional month, their levels declined in the IFN-gamma treated group. These findings were in concordance with an increased glomerular deposition of immune complexes in the IFN-gamma treated mice. IFN-gamma upregulated the levels of IL-4 and increased the number of IL-4 and IL-6 secreting splenocytes. In conclusion IFN-gamma administration can aggravate the clinical and laboratory outcome of 16/6 id induced lupus in BALB/c mice.
引用
收藏
页码:445 / 454
页数:10
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