1629 PRODUCTION OF THE LYMPHOKINE, SOLUBLE IMMUNE RESPONSE SUPPRESSOR (SIRS) BY PATIENTS WITH NEPHROTIC SYNDROME

Abstract

Nephrotic patients often show suppressed immune responsiveness of unknown origin. At the last SPR meeting we reported that patients with active minimal change nephrotic syndrome (MCNS) or membranoproliferative glomerulonephritis (MPGN) excrete SIRS in their urine. This lymphokine, produced in vitro by interferon- or mitogen-activated suppressor T cells, inhibits division by normal and neoplastic cells and antibody secretion by B lymphocytes. SIRS activity disappears from urine after initiation of steroid therapy but before remission of nephrosis. To determine whether increased serum SIRS levels are also associated with these diseases, sera from four patients (3MCNS, 1MPGN) were assayed for SIRS activity. Patient sera, but not control sera, suppressed immunoglobulin production by pokeweed mitogen-activated lymphocytes by 55–70% at a final concentration of 2-10% in culture; suppressive activity was absorbed from serum by monoclonal anti-SIRS antibody. Lymphocytes obtained from two patients (1MCNS, 1MPGN) produced SIRS without requiring activation by exogenous agents. These data suggest that lymphocytes of nephrotic patients with MCNS or MPGN are continuously producing SIRS. This may account for the increased levels of SIRS in sera and urine and may also account for immunosuppression in these patients. Finally, hydrocortisone (10⁻⁶ to 10⁻⁷M) inhibited production of SIRS by activated lymphocytes; this may explain cessation of SIRS excretion after initiation of steroid therapy.

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