Urinary excretion of interleukin-6 correlates with proteinuria in acute Puumala hantavirus-induced nephritis

Abstract

Background: Nephropathia epidemica (NE) is a mild type of hemorrhagic fever with renal syndrome caused by Puumala Hantavirus. Cytokines are thought to have an important role in the pathogenesis of NE. The aim of this study is to evaluate whether cytokines contribute to renal involvement in NE. Methods: Overnight urinary excretion of interleukin-1β (IL-1β), IL-1 receptor antagonist (IL-1Ra), IL-6, tumor necrosis factor-α (TNF-α), albumin, immunoglobulin G (IgG), and α1-microglobulin and quantitative 24-hour urinary protein excretion were measured for 3 consecutive days from 70 hospitalized patients with acute NE (49 men, 21 women; age, 15 to 70 years; median age, 39 years). Plasma levels of the respective cytokines also were measured. Urinary collections were repeated after 1 year. The control group for blood samples included 400 healthy blood donors. Results: Maximum median urinary IL-6 excretion in the acute phase of NE was increased compared with values detected after 1 year (49.5 versus 0.7 pg/min; P < 0.001). Correspondingly, maximum median plasma IL-6 concentration in patients was increased compared with controls (14.6 versus 1.2 pg/mL; P < 0.001). Urinary IL-6 excretion correlated with urinary albumin, IgG, and protein excretion (r = 0.79; P < 0.001; r = 0.76; P < 0.001; and r = 0.65; P < 0.001, respectively), but not plasma IL-6 levels (r = 0.18; P = 0.148). Conclusion: Plasma IL-6 concentrations and urinary IL-6 excretion were markedly increased in patients with acute NE, but there was no correlation between plasma and urinary IL-6 levels. The high urinary IL-6 levels might reflect local production of this proinflammatory cytokine in the kidneys during acute infection.