A novel and effective approach of developing aggressive experimental autoimmune gastritis in neonatal thymectomized BALB/c mouse by polyinosinic:polycytidylic acid.
Neonatal thymectomy induces autoimmune gastritis (AIG) in 40-70% of BALB/c mice. We presumed that induction of autoimmunity by polyinosinic:polycytidylic acid (poly I:C) might allow development of a more aggressive model of AIG. A group of BALB/c mice were thymectomized on day 3 after birth. Neonatal thymectomized mice were either injected with poly I:C or phosphate-buffered saline (PBS). Non thymectomized neonatal BALB/c mice were injected with only poly I:C. All neonatal thymectomized mice injected with poly I:C developed 3 cardinal features of AIG: (1) moderate to severe degree gastritis (2) presence of autoantibody to H(+)/K(+) ATPase and (3) loss of parietal cells. However, only 70% of the PBS-treated neonatal thymectomized BALB/c mice developed some, but not, all features of AIG. A mild degree of AIG was seen in 12 of 31 nonthymectomized BALB/c mice administered with only poly I:C. Administration of poly I:C in neonatal thymectomized BALB/c mice in the first and second week appeared to be the most effective for induction of aggressive AIG. The levels of interleukin (IL)-6, IL-12p70, interferon-gamma and tumour necrosis factor-alpha were significantly higher in poly I:C-injected thymectomized mice compared to PBS-injected neonatal thymectomized mice (P < 0.05). The frequencies of CD4(+)CD25(+) regulatory T cells in the spleen were significantly decreased in neonatal thymectomized mice administered with poly I:C compared to PBS-treated neonatal thymectomized mice (P < 0.01). Taken together, these results suggest that induction of inflammatory cytokines and reduction of regulatory T cells by poly I:C might contribute to the development of an aggressive model of AIG in neonatal thymectomized BALB/c mice.
Kobayashi
Y
Y
Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
Murakami
H
H
Akbar
S M F
SM
Matsui
H
H
Onji
M
M
D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000097:blood; D005756:Gastritis / Q000276:immunology / Q000473:pathology; D017506:H(+)-K(+)-Exchanging ATPase / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010295:Parietal Cells, Gastric / Q000276:immunology / Q000473:pathology; D011070:Poly I-C; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013934:Thymectomy
D001323:Autoantibodies; D016207:Cytokines; D017506:H(+)-K(+)-Exchanging ATPase; D011070:Poly I-C