title: Collagen-induced arthritis is exacerbated in C-reactive protein-deficient mice.
abstract: OBJECTIVE
  Blood C-reactive protein (CRP) is routinely measured to gauge inflammation. In rheumatoid arthritis (RA), a heightened CRP level is predictive of a poor outcome, while a lowered CRP level is indicative of a positive response to therapy. CRP interacts with the innate and adaptive immune systems in ways that suggest it may be causal in RA and, although this is not proven, it is widely assumed that CRP makes a detrimental contribution to the disease process. Paradoxically, results from animal studies have indicated that CRP might be beneficial in RA. This study was undertaken to study the role of CRP in a mouse model of RA, the collagen-induced arthritis (CIA) model.
  
  
  METHODS
  We compared the impact of CRP deficiency with that of transgenic overexpression of CRP on inflammatory and immune responses in mice, using CRP-deficient (Crp-/-) and human CRP-transgenic (CRP-Tg) mice, respectively. Susceptibility to CIA, a disease that resembles RA in humans, was compared between wild-type, Crp-/-, and CRP-Tg mice.
  
  
  RESULTS
  CRP deficiency significantly altered the inflammatory cytokine response evoked by challenge with endotoxin or anti-CD3 antibody, and heightened some immune responses. Compared to that in wild-type mice, CIA in Crp-/- mice progressed more rapidly and was more severe, whereas CIA in CRP-Tg mice was dramatically attenuated. Despite these disparate clinical outcomes, anticollagen autoantibody responses during CIA did not differ among the genotypes.
  
  
  CONCLUSIONS
  CRP exerts an early and beneficial effect in mice with CIA. The mechanism of this effect remains unknown but does not involve improvement of the autoantibody profile. In humans, the presumed detrimental role of a heightened blood CRP level during active RA might be balanced by a beneficial effect of the baseline CRP (i.e., levels manifest during the preclinical stages of disease).
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Jones
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Pegues
authors.forename: Mark A
authors.initials: MA
authors.lastname: McCrory
authors.forename: Steven W
authors.initials: SW
authors.lastname: Kerr
authors.forename: Huiping
authors.initials: H
authors.lastname: Jiang
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Sellati
authors.forename: Valentina
authors.initials: V
authors.lastname: Berger
authors.forename: Jorge
authors.initials: J
authors.lastname: Villalona
authors.forename: Rajvee
authors.initials: R
authors.lastname: Parikh
authors.forename: Mary
authors.initials: M
authors.lastname: McFarland
authors.forename: Lynn
authors.initials: L
authors.lastname: Pantages
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Madwed
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Szalai
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D002097:C-Reactive Protein / Q000235:genetics*; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012720:Severity of Illness Index
chemical_list: D016207:Cytokines; D002097:C-Reactive Protein