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C‐reactive protein (CRP) is an acute‐phase serum protein with binding reactivity to nuclear autoantigens and immunomodulatory function. The MRL/lpr mouse is an important model of human systemic lupus erythematosus (SLE). These mice develop high‐titer anti‐DNA antibodies and immune complex–mediated nephritis and exhibit progressive lymphadenopathy. The mortality rate among these mice is 50% by age 18–20 weeks; the most frequent cause of death is glomerulonephritis. The present study was undertaken to determine whether treatment of mice with CRP would affect the course of lupus nephritis.MRL/lpr mice were treated with a single 200‐μg injection of CRP at either age 6 weeks (before disease onset) or age 13 or 15 weeks (when proteinuria had reached high levels). Proteinuria was measured weekly, and levels of anti–double‐stranded DNA autoantibodies and blood urea nitrogen were determined monthly. Glomerular immune complex deposition and renal pathology were assessed in mice ages 15 weeks and 17 weeks.Early CRP treatment markedly delayed the onset of proteinuria and lymphadenopathy, increased survival, and reduced levels of autoantibodies to DNA. Treatment of mice with active disease reversed proteinuria and prolonged survival. Renal disease was decreased in CRP‐treated mice, with a marked suppression of glomerular pathology, tubular degeneration, and interstitial inflammation, which correlated with the decrease in proteinuria and azotemia.These findings demonstrate that systemic suppression of autoimmunity is initiated by a single injection of CRP. Long‐term maintenance of CRP‐mediated protection was reversed by injection of an anti‐CD25 monoclonal antibody but not by macrophage depletion, suggesting that disease suppression is maintained by CD25‐bearing T cells. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]