Dependence on interferon-gamma for the spontaneous occurrence of arthritis in DBA/1 mice.
OBJECTIVE
Male DBA/1 mice are known to spontaneously develop arthritis in the hind legs. The present study was undertaken to investigate the role of endogenous interferon-gamma (IFNgamma) in the pathogenesis of this ankylosing enthesopathy.


METHODS
The role of IFNgamma was studied by examining the development of arthritis in IFNgamma receptor-knockout (IFNgammaR-KO) DBA/1 mice as compared with wild-type mice, and by treatment of wild-type mice with monoclonal anti-IFNgamma antibody. IFNgamma-disrupted and wild-type mice were mixed and housed in the same cage, and clinical symptoms of arthritis were assessed weekly for at least 9 weeks. Histologic examination was performed at the end of the experiment.


RESULTS
In DBA/1 wild-type mice, 70% of the animals developed clinical symptoms of spontaneous arthritis, such as redness and swelling of the proximal interphalangeal joints, toe stiffness, and ankylosis. As evident from microscopic evaluation, the arthritis was mainly characterized by formation of new cartilage and bone, originating at the entheses and leading to ankylosis. The incidence and severity of arthritis, both clinically and histologically, were significantly reduced in IFNgammaR-KO mice. In wild-type mice, neutralizing anti-IFNgamma antibody inhibited the occurrence of the disease for the duration of treatment.


CONCLUSIONS
The results suggest that endogenous IFNgamma plays an important role in the initial stages of spontaneous arthritis, and that the inflammatory components in its pathogenesis are more prominent than has been believed. In view of the similarity between this disease and spondylarthropathies in humans, the data suggest that endogenous IFNgamma may also play a disease-promoting role in the human condition and thus may serve as a target for therapy.
Matthys
Patrick
P
University of Leuven, Leuven, Belgium. Patrick.Matthys@rega.kuleuven.ac.be
Lories
Rik J
RJ
De Klerck
Bert
B
Heremans
Hubertine
H
Luyten
Frank P
FP
Billiau
Alfons
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001168:Arthritis / Q000453:epidemiology / Q000503:physiopathology* / Q000628:therapy; D015994:Incidence; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D012720:Severity of Illness Index; D015398:Signal Transduction
D000906:Antibodies; D007371:Interferon-gamma