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


CONCLUSIONS
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.
Rodriguez
Wilfredo
W
University of New Mexico School of Medicine, Albuquerque, USA.
Mold
Carolyn
C
Kataranovski
Milena
M
Hutt
Julie
J
Marnell
Lorraine L
LL
Du Clos
Terry W
TW
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000627:therapeutic use*; D004247:DNA / Q000276:immunology; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D016753:Interleukin-10 / Q000502:physiology; D007678:Kidney Glomerulus / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000188:drug therapy*
D001323:Autoantibodies; D007074:Immunoglobulin G; D016753:Interleukin-10; D002097:C-Reactive Protein; D004247:DNA