title: Pulmonary inflammation in mice with collagen-induced arthritis is conditioned by complete Freund's adjuvant and regulated by endogenous IFN-γ.
abstract: Following immunization with collagen II (CII) in complete Freund's adjuvant (CFA), DBA/1 mice develop arthritis of major joints. This collagen-induced arthritis (CIA) is used as a model for rheumatoid arthritis (RA) in man. Inflammatory changes in lung tissue commonly occur in RA. However, evidence for pulmonary inflammation in CIA is scarce and ambiguous. Here, we demonstrate pulmonary inflammation accompanying CIA in wild-type DBA/1 mice. In IFN-γ receptor-deficient (IFN-γR KO) mice, inflammation was more frequent and more severe. Injection of CFA only (without CII) proved to be as efficient in eliciting pulmonary inflammation as immunization with CFA + CII, though being less effective in causing arthritis. Significant correlation in severity between joint and pulmonary involvement could not be demonstrated. Macroscopic, microscopic, and functional characteristics of pulmonary inflammation in the mice resembled those seen in human RA. Increased inflammation in IFN-γR KO mice was accompanied by augmented expression of various cytokines and chemokines, as measured by RT-PCR on affected tissue. Treatment with a TNF-α inhibitor ameliorated lung pathology. We conclude that CIA in DBA/1 mice is accompanied by pulmonary inflammation. Although both disease processes are kept in check by endogenous IFN-γ, lack of strict parallelism indicates that overlap in their pathogeneses is partial.
authors.affiliation: Laboratory of Immunobiology, Rega Institute, University of Leuven, Leuven, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Schurgers
authors.forename: Freya
authors.initials: F
authors.lastname: Mertens
authors.forename: Jeroen A J
authors.initials: JA
authors.lastname: Vanoirbeek
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Put
authors.forename: Tania
authors.initials: T
authors.lastname: Mitera
authors.forename: Ellen
authors.initials: E
authors.lastname: De Langhe
authors.forename: Alfons
authors.initials: A
authors.lastname: Billiau
authors.forename: Peter H M
authors.initials: PH
authors.lastname: Hoet
authors.forename: Benoit
authors.initials: B
authors.lastname: Nemery
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthys
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D005620:Freund's Adjuvant / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D007371:Interferon-gamma; D005620:Freund's Adjuvant