Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Lung Inflammation and Pulmonary Function Alterations in Collagen-Induced Arthritis and in the Absence of Interferon-gamma Signaling.

Schurgers1,  Evelien, Mertens2,  Freya, Vanoirbeek3,  Jeroen, Mitera2,  Tania, Put2,  Stéphanie, Nemery3,  Benoit, Matthys2,  Patrick

Laboratory of Immunobiology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium
Laboratory of Immunobiology, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium
Research Unit of Lung Toxicology (Laboratory of Pneumology), Katholieke Universiteit Leuven, Leuven Belgium

Background:

Rheumatoid arthritis (RA), a systemic inflammatory disease affecting the joints, is regularly associated with extra-articular symptoms. Lung complications are one of these manifestations and have a profound impact on patient well-being and survival. There are no reports on pulmonary complications in collagen-induced arthritis (CIA), a widely used animal model for RA. We investigated potential lung inflammation and changes in pulmonary functions during CIA, using both wild type and interferon-gamma (IFN-g) receptor knock-out (IFN-gR KO) mice, which develop a more severe form of arthritis.

Methods:

CIA was induced in mice by a subcutaneous injection of collagen type II in Freund's adjuvant. At various time points after induction, cytokine and chemokine expression in the lungs and in synovial tissues were analysed by qPCR. Cell influx in the airways and inflammation in lung tissue were determined by broncheoalveolar lavage (BAL) and histology, respectively. To analyse the impact of arthritis on lung physiology, lung function measurements were assessed via the invasive forced oscillation technique of the flexiVent system. Resistance and elastance of the whole lung and more specific, the large airways and the alveoli were measured.

Results:

Upon induction of CIA, the onset of arthritic symptoms was accompanied by induction of interleukin-1b (IL-1b) and the neutrophil chemokine Granulocyte Chemotactic Protein 2 (GCP-2) in the synovial tissues of both wild type and IFN-gR KO mice. In the lungs of wild type mice, IL-1b levels became detectable at day 10, before the onset of arthritis. In arthritic IFN-gR KO mice, lungs expressed GCP-2 and other chemokines such as KC and Monocyte Chemotactic Protein 1 (MCP-1). BAL fluid of arthritic wild type and IFN-gR KO mice contained elevated numbers of cells as compared to their respective naïve counterparts. The increase in cell numbers was caused by influx of macrophages and lymphocytes. BAL fluid of immunized IFN-gR KO mice showed an additional influx of neutrophils. On histological examination, lungs of arthritic IFN-gR KO mice demonstrated a perivascular lymphocytic infiltration into the lung tissue which was absent in arthritic wild type mice and in naïve animals. When lung function measurements were performed, tissue elasticity (H) and resistance (Rn) of the lungs were significantly elevated in arthritic IFN-gR KO mice as compared to naïve mice. No such effects could be observed in wild type mice.

Conclusions:

Lung manifestations, as evident from expression of pro-inflammatory cytokines and chemokines in lung tissue and from cell influx in BAL, were detectable in both wild type and IFN-gR KO mice after induction of CIA. Perivascular infiltration into the lung tissue was exclusively present in arthritic IFN-gR KO mice and these changes negatively influenced the function of the lungs since these mice presented with a more rigid lung tissue. These results demonstrate that pulmonary manifestations do exist in CIA, and become more manifest upon deletion of one single gene (in this case IFN-g). Therefore, CIA may prove a useful animal model to study the association between inflammation in the joints and in the lungs, as seen in RA patients.

To cite this abstract, please use the following information:
Schurgers, Evelien, Mertens, Freya, Vanoirbeek, Jeroen, Mitera, Tania, Put, Stéphanie, Nemery, Benoit, et al; Lung Inflammation and Pulmonary Function Alterations in Collagen-Induced Arthritis and in the Absence of Interferon-gamma Signaling. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1720
DOI: 10.1002/art.29485

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