MONOCYTE CHEMOATTRACTANT PROTEIN-1 IS EXCRETED IN EXCESSIVE AMOUNTS IN THE URINE OF PATIENTS WITH LUPUS NEPHRITIS

BACKGROUND: In patients with lupus nephritis, mononuclear inflammatory cells infiltrate the renal interstitium and glomeruli, and the degree of leukocyte infiltration correlates with the severity of the renal d ysfunction. The precise mediator signaling inflammatory cells to migra te into the kidney is not known. Recent findings that monocyte chemoat tractant protein-1 (MCP 1), a chemotactic cytokine with a high degree of specificity for lymphocytes and monocytes, is overexpressed in glom eruli from rats with immunocomplex glomerulonephritis prompted us to e xplore the possibility that MCP-1 could be implicated in the renal inf lammatory response of lupus erythematosus. EXPERIMENTAL DESIGN: Serum and urine levels of MCP-1 were evaluated in 10 patients with active lu pus nephritis. Patients were studied at admission, before therapy, and at various time points after the first administration of high dose me thylprednisolone. There was an additional observation of the four pati ents who underwent remission of clinical signs of the disease after ch ronic steroid treatment. Three additional groups, one (n = 9) of patie nts with inactive lupus nephritis, one (n = 9) of patients with nonlup us glomerulonephritis and high degree proteinuria, and one (n = 10) of healthy subjects, were also studied.RESULTS: In patients with active lupus nephritis, urinary MCP-1 was significantly higher than in lupus patients studied in the inactive phase of the disease or in healthy vo lunteers. High doses of i.v. methylprednisolone significantly lowered urinary MCP-1 in patients with active lupus nephritis. In patients und ergoing remission of lupus nephritis after chronic steroid treatment, urinary MCP-1 levels were comparable to those found in healthy control s. A strong positive correlation was found between MCP-1 urinary excre tion levels and leukocyte infiltration in the kidney, and urinary MCP- 1 did not correlate with either serum MCP-1 levels or proteinuria. Unl ike in lupus, in patients with nonlupus forms of glomerulonephritis, u rinary RICP-1 was comparable to controls. CONCLUSIONS: Altogether, the present data suggest a role for MCP-1 in mononuclear cell migration i nto the kidney in lupus nephritis.