Alum, an aluminum-based adjuvant, induces Sjögren's syndrome-like disorder in mice.

OBJECTIVES: Adjuvant-induced innate immune responses have been suspected to play a role in the initiation of certain autoimmune disorders. This study investigates the role of alum, an aluminum-based adjuvant in the induction of Sjögren's syndrome-like disorder in mice. METHODS: Inbred, female New Zealand Mixed (NZM) 2758 strain of mice were injected with alum. Control mice were treated similarly with PBS. The mice were monitored for salivary gland dysfunction by measuring pilocarpine-induced salivation. Presence of lymphocytic infiltrates within the submandibular glands was studied by histopathology. Autoantibodies to Ro and La proteins were analysed by ELISA and the presence of anti-nuclear antibodies (ANA) was analysed by indirect immunofluorescence. RESULTS: By eight weeks after treatment, the saliva production in the alum-treated mice was significantly decreased in comparison to the PBS-treated mice. This functional loss persisted till the termination of experiments at 20 wks. The incidence and severity of sialoadenitis was significantly higher in the alum-treated mice. Although there were no differences in the levels of anti-Ro/La autoantibodies in sera of alum and PBS-treated groups, the alum group showed higher ANA reactivity. CONCLUSIONS: In the NZM2758 mice, alum induces a Sjögren's syndrome-like disorder that is characterised by chronic salivary gland dysfunction and the presence of lymphocytic infiltrates within the salivary glands. Thus, the potential of aluminum-based adjuvants for induction of autoimmunity should be closely monitored in individuals genetically susceptible to developing autoimmune disorders.

Activation of innate immunity accelerates sialoadenitis in a mouse model for Sjögren's syndrome-like disease.

OBJECTIVE: Sjögren's syndrome is a chronic autoimmune disorder characterized by progressive lymphocytic infiltration within the salivary and lacrimal glands. This study was undertaken to investigate the effects of innate immunity activation on sialoadenitis in a mouse strain genetically susceptible for development of SS-like disease. METHODS: Female New Zealand Black X New Zealand White F1 mice were repeatedly treated with toll-like 3 receptor agonist poly(I:C). Submandibular glands were investigated at different time points for sialoadenitis by immunohistochemistry and for gene expression of different chemokines by quantitative PCR. Submandibular gland-infiltrating cells were characterized by flow cytometry. RESULTS: Poly(I:C) treatment significantly upregulated the expression of multiple chemokines within the submandibular glands. The severity and incidence of sialoadenitis was considerably higher in poly(I:C)-treated mice. There was a preponderance of dendritic cells and NK cells in the initial inflammatory cell infiltrates, and these were followed by CD4+ T cells. CONCLUSIONS: Our data clearly demonstrate that systemic activation of innate immunity accelerates sialoadenitis in a mouse model for SS-like disease. These findings suggest that chronic activation of innate immunity can influence certain features of SS.