Reversal of ongoing proteinuria in autoimmune mice by treatment with C-reactive protein

Arthritis Rheum. 2005 Feb;52(2):642-50. doi: 10.1002/art.20846.

Abstract

Objective: To examine the ability of injection of C-reactive protein (CRP) to treat systemic lupus erythematosus (SLE) in the (NZB x NZW)F(1) (NZB/NZW) mouse and to use a nephrotoxic nephritis (NTN) model to further examine the mechanism of this activity.

Methods: NZB/NZW mice were given a single injection of 200 mug of CRP prior to disease onset or after the onset of high-grade proteinuria. Mice were monitored weekly for proteinuria and monthly for anti-double-stranded DNA (anti-dsDNA) antibodies. NTN was induced by immunization with rabbit IgG followed by rabbit anti-mouse glomerular basement membrane. Proteinuria was measured daily, and renal pathology was scored. CRP was injected at the time of disease induction or 9 days later.

Results: Treatment of NZB/NZW mice with CRP prior to disease onset delayed the onset of high-grade proteinuria by 16 weeks (P < 0.0001) and prolonged survival by 13 weeks (P < 0.002). CRP treatment of NZB/NZW mice during acute disease rapidly decreased proteinuria, and the treated mice remained aproteinuric for at least 10 weeks. Control and CRP-treated mice developed similar levels of anti-dsDNA. In C57BL/6 mice, injection of CRP either before or after induction of NTN suppressed proteinuria and glomerular pathology. CRP was completely ineffective in treating NTN in interleukin-10 (IL-10)-deficient mice.

Conclusion: CRP injection suppresses inflammation in the kidney in SLE and NTN. The requirement for IL-10 in this protection suggests that CRP must rapidly initiate an IL-10-dependent antiinflammatory process. These findings suggest that a major function of CRP during the acute-phase response is to limit tissue damage and modulate acute inflammation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Autoimmune Diseases / drug therapy*
  • C-Reactive Protein / therapeutic use*
  • DNA / immunology
  • Female
  • Immunization
  • Immunoglobulin G / immunology
  • Interleukin-10 / physiology
  • Kidney Glomerulus / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NZB
  • Proteinuria / drug therapy*

Substances

  • Autoantibodies
  • Immunoglobulin G
  • Interleukin-10
  • C-Reactive Protein
  • DNA