Interleukin-12 induces salivary gland dysfunction in transgenic mice, providing a new model of Sjögren's syndrome.
OBJECTIVE
Interleukin-12 (IL-12) is a pleiotropic cytokine that is elevated in the affected organs of patients with Sjögren's syndrome (SS). We have previously reported that overexpression of IL-12 in CBA mice leads to mononuclear infiltration of salivary and lacrimal glands, as well as to expansion of bronchial lymphoid tissue and decreased mucociliary clearance. Because xerostomia is one of the most important clinical features in SS patients, our main objective in the current study was to evaluate salivary gland function in IL-12-transgenic mice. Our secondary objective was to further characterize this animal model and to determine if the changes observed in these mice are representative of those observed in patients with SS overall.


METHODS
Pilocarpine-stimulated salivary flow was used to address salivary gland function in a large group of IL-12-transgenic mice bred onto the autoimmune-prone SJL background. Furthermore, salivary glands were removed to assess the formation of infiltrates in the glands and gland morphology. Serum was also collected from these animals to investigate the formation of autoantibodies.


RESULTS
Pilocarpine-stimulated salivary flow was significantly lower in IL-12-transgenic mice than in wild-type controls. Salivary glands from transgenic mice exhibited an increase in both the number and the size of lymphocytic foci, versus glands from age-matched controls. Furthermore, the acini in transgenic mice were fewer in number and larger in size compared with acini in controls. An age-dependent increase in anti-SSB/La antibodies was observed in IL-12-transgenic mice and was accompanied by an increase in antinuclear antibodies.


CONCLUSIONS
Our findings indicate that a number of conditions associated with SS are exhibited by IL-12-transgenic SJL mice and that this model might be useful in researching multiple aspects of the disease.
Vosters
Jelle L
JL
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, USA.
Landek-Salgado
Melissa A
MA
Yin
Hongen
H
Swaim
William D
WD
Kimura
Hiroaki
H
Tak
Paul P
PP
Caturegli
Patrizio
P
Chiorini
John A
JA
D000818:Animals; D000974:Antibodies, Antinuclear; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000235:genetics; D049108:Cell Enlargement; D049109:Cell Proliferation; D018678:Cholinergic Agents; D004195:Disease Models, Animal; D005260:Female; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010862:Pilocarpine; D012469:Salivary Glands / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012737:Sex Factors; D012859:Sjogren's Syndrome / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*
D000974:Antibodies, Antinuclear; D015415:Biomarkers; D018678:Cholinergic Agents; D010862:Pilocarpine; D018664:Interleukin-12