To examine the ability of injection of C-reactive protein (CRP) to treat systemic lupus erythematosus (SLE) in the (NZB × NZW)F1 (NZB/NZW) mouse and to use a nephrotoxic nephritis (NTN) model to further examine the mechanism of this activity.
NZB/NZW mice were given a single injection of 200 μg 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.
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.
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.