Immunomodulation of murine experimental SLE-like disease by interferon-gamma.
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.
Amital
H
H
Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel.
Levi
Y
Y
Blank
M
M
Barak
V
V
Langevitz
P
P
Afek
A
A
Nicoletti
F
F
Kopolovic
J
J
Gilburd
B
B
Meroni
P L
PL
Shoenfeld
Y
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000378:metabolism; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000097:blood / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D007371:Interferon-gamma