title: The evolving systemic and local biomarker milieu at different stages of disease progression in rat collagen-induced arthritis.
abstract: Rats with collagen-induced arthritis (CIA) were necropsied on 14 occasions from 4 days after induction to 27 days after disease onset to evaluate the kinetics of local (joint protein extracts) and systemic (serum) levels of inflammatory and pro-erosive factors. Systemic increases in alpha1 acid glycoprotein and KC/GRO together with systemic and local enrichment of interleukin (IL)-1beta, IL-6, CCL2, transforming growth factor (TGF)-beta and elevated IL-1alpha and IL-18 in joint extracts preceded the onset of clinical disease. Systemic upregulation of IL-1beta, IL-6, TGF-beta CCL2, RANKL and prostaglandin E(2) (PGE(2)) during acute and/or chronic CIA coincided with systemic leukocytosis and a CD4+ T-cell increase in blood and spleen. In contrast, progression of joint erosions during clinical CIA was associated with intra-articular increases in IL-1alpha/beta, IL-6, IL-18, CCL2, KC/GRO and RANKL, and a dramatic decline in osteoprotegerin (OPG). These data indicate that systemic and local events in inflammatory arthritis can be discrete processes, driven by multiple cellular and humoral mediators with distinct temporospatial profiles.
authors.affiliation: Department of Metabolic Disorders, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. mstolina@amgen.com
authors.forename: Marina
authors.initials: M
authors.lastname: Stolina
authors.forename: Brad
authors.initials: B
authors.lastname: Bolon
authors.forename: Denise
authors.initials: D
authors.lastname: Dwyer
authors.forename: Scot
authors.initials: S
authors.lastname: Middleton
authors.forename: Diane
authors.initials: D
authors.lastname: Duryea
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kostenuik
authors.forename: Ulrich
authors.initials: U
authors.lastname: Feige
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Zack
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes; D003094:Collagen; D016207:Cytokines / Q000032:analysis; D018450:Disease Progression; D007107:Immune System; D007249:Inflammation; D018836:Inflammation Mediators / Q000032:analysis; D007700:Kinetics; D007964:Leukocytosis; D051381:Rats; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D003094:Collagen