Polarization Toward Th1-Type Response in Active, but Not in Inactive, Lupus Inhibits Late Allergic Rhinitis in Lupus-Pro
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Polarization Toward Th1-Type Response in Active, but Not in Inactive, Lupus Inhibits Late Allergic Rhinitis in Lupus-Prone Female NZB×NZWF1 Mice Toshiharu Hayashi(1,2,3 and Ayumi Murase1
Abstract—The association of allergic diseases and disease activity in systemic lupus erythematosus (SLE, lupus) is controversial. The study investigates lupus activity-related differences in the induction of late allergic rhinitis (LAR) in the female NZB×NZW(B/W)F1 mouse model for lupus. The LAR, which is induced by ovalbumin, was examined during the preactive (before clinical onset) and active (after clinical onset) phases in mice. Induction of LAR was less severe in mice with active lupus in contrast to clinically healthy lupus mice that developed a more severe allergic rhinitis. Inhibition of the development of LAR may be due to reduced eosinophilia and local interleukin-4 secretion during active autoimmune disease. In addition, systemic interferon-γ, but not IL-4, production increased during the active phase, but not the preactive phase. This suggests that the predominating Th1 lineage commitment in mice with active lupus may be responsible for the inhibition of the allergic Th2 response. The present study may shed some light on the controversy of the prevalence of allergic diseases in SLE patients. KEY WORDS: late allergic rhinitis; Th1/Th2; cytokines; lupus; B/WF1 mouse.
INTRODUCTION Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by the production of several non-organ-specific autoantibodies such as anti-nuclear, anti-dsDNA, and antiphospholipid antibodies [1, 2]. Immune complex (IC) deposition in renal capillaries, which is one of the primary pathological findings of SLE, leads to glomerulonephritis [3, 4]. Female B/WF1 mice, a popular murine model for human SLE, spontaneously develop a systemic autoimmune disorder with age [5, 6]. In addition, helper Th1 cytokines may play a role in the pathogenesis in lupus nephritis [7–12]. On the other hand, allergic rhinitis, 1
Laboratory of Veterinary Pathology, Faculty of Joint Veterinary Medicine, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 7538515, Japan 2 Laboratory of Veterinary Pathology, Faculty of Agriculture, Yamaguchi University, 1677-1, Yoshida, Yamaguchi 753-8515, Japan 3 To whom correspondence should be addressed at Laboratory of Veterinary Pathology, Faculty of Agriculture, Yamaguchi University, 1677-1, Yoshida, Yamaguchi 753-8515, Japan. E-mail: hayasi@ yamaguchi-u.ac.jp
which is mediated by Th2 cells, involves a two-phase allergic reaction: early and/or late phases. In the early phase, IgE-sensitized mast cells and basophils that interacted with allergens degranulate and release mediators such as histamine and leukotriene, whereas the late phase of the allergic response mainly involves infiltration of eosinophils and Th2 cells producing interleukin (IL)-4, IL-5, and IL-13 in nasal mucosa [13–16]. After reports of higher rates of allergy in SLE, there has been much interest in the relation between IgEmediated allergy and t
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