title: Responses of the rat immune system to arthritogenic adjuvant oil.
abstract: T-cell mediated inflammatory joint diseases with similarities to rheumatoid arthritis (RA) can be triggered in arthritis-prone rat strains by intradermal injection of adjuvant oils. The pathogenesis of oil-induced arthritis (OIA) remains elusive, and a largely unresolved question is how the rat immune system responds to arthritogenic oils such as incomplete Freund's adjuvant (IFA). Here we report that IFA already induces increased plasma levels of the acute-phase reactants (APR) fibrinogen and alpha1-acid glycoprotein at day 4 postinjection (p.i). In contrast, no early responses were detected in the joints before infiltration of the T cells, which coincided with arthritis onset at 11-14 days post injection (d.p.i.) The infiltrating cells were possibly derived from draining lymph nodes (LN), which were hyperplastic and contained increased cell numbers from 4 days p.i. and onwards. The magnitude of the early increase in cell numbers and APR was regulated by non-major histocompatibility complex (MHC) genes, as determined by comparison between arthritis-susceptible DA rats and arthritis-resistant but MHC-identical LEW.lAV1 and PVG.1AV1 rats. Arthritisprone DA rats developed a weak acute-phase response, suggesting that this systemic response may be counteracting disease. The DA rats also had the largest early increase in LN-cell numbers, suggesting that the LN hyperplasia is part of a disease pathway. The analysis of hyperplastic LN after in vivo labelling with bromodeoxyuridine (BrdU) revealed increased numbers and proportions of proliferating lymphocytes, including T cells. Furthermore, polymerase chain reaction (PCR)-analysis of LN cytokine mRNA revealed upregulation of interleukin (IL)-1beta at 4 d.p.i. We conclude that adjuvant oil exposure triggers both systemic acute phase reactions and local activation of the peripheral lymphoid system. These responses are genetically regulated and may determine arthritis development and susceptibility.
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Lena.Svelander@cmm.ki.se
authors.forename: L
authors.initials: L
authors.lastname: Svelander
authors.forename: B C
authors.initials: BC
authors.lastname: Holm
authors.forename: A
authors.initials: A
authors.lastname: Buchtt
authors.forename: J C
authors.initials: JC
authors.lastname: Lorentzen
mesh_terms: D000210:Acute-Phase Reaction; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D002455:Cell Division; D016207:Cytokines / Q000235:genetics; D005340:Fibrinogen / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D009961:Orosomucoid / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D016207:Cytokines; D009961:Orosomucoid; D012333:RNA, Messenger; D005340:Fibrinogen