Low levels of interleukin-1 receptor antagonist coincide with kidney involvement in systemic lupus erythematosus

The objective was to study the relationship between the levels of interleukin-l receptor antagonist (IL-1Ra) and disease activity and the acute-phase response in SLE patients with and without renal involvement. Twenty SLE patients who had distinct active clinical manifestations.(eight gromerulonephritis, four systemic vasculitis without kidney involvement, nine skin gash, 12 arthritis, five serositis, four neuropsychiatric manifestations, three-thrombocytopenia, one myositis and one haemolytic anaemia) were studied during a period of 8-12 months. Serum and plasma samples were taken at intervals of 6 weeks-4 months and tested for IL-1Ra, IL-1 beta, IL-6, IgG and anti-dsDNA, Clq, C3, C4 and C-reactive protein (CRP). IL-1Ra serum concentrations were increased in most SLE patients with active disease when compared to normal blood donors. However, at the time of flare, significantly higher levels of IL-1Ra were observed in patients with extra-renal disease as compared to other patients (median [range]: 363 [202-3041] and 4847 [268-27180] pg/ml for patients with and without renal involve ment, respectively). This difference was not due to proteinuria. IL-1Ra levels did not correlate with SLEDAI score during flares; but they were elevated during flares in patients with extra-renal manifestations. When disease activity was at its highest, IL-1Ra concentrations correlated with IL-1 beta (r = 0.76; P<0.001), IL-6 (r = 0.60; P<0.01) and CRP (r = 0.61; P<0.01), but not with Clq, C3, C4 and anti-dsDNA levels. The study showed that the pattern of inflammatory cytokines in active SLE varies in a manner that is dependent on which organs are involved. A relative absence of IL-1Ra response appears to be a feature characteristic of kidney involvement. IL-1Ra elevation clearly correlates with flares involving other organs.