Defective Spontaneous and Bacterial Lipopolysaccharide-Stimulated Production of Interleukin-1 Receptor Antagonist by Polymorphonuclear Neutrophils of Patients With Active Systemic Lupus Erythematosus

Abstract

Interleukin-1 receptor antagonist (IL-1ra) binds competitively to IL-1 receptors but does not transduce the signal which blocks the biological activities induced by IL-1. In this study, polymorphonuclear neutrophils (PMN) and mononuclear cells (MNC) from the patients with active systemic lupus erythematosus (SLE) (n = 11), inactive SLE (n = 13) and normal individuals (n = 13) were compared for the IL-1ra producing capacity of these cells. PMN and MNC at a concentration of 1 x 10(6) cells/ml were incubated with medium alone (spontaneous) or stimulated with lipopolysaccharide (LPS, 100 ng/ml) for 24 h. The IL-1ra concentration in the supernatants was quantified by ELISA method. Both spontaneous and LPS-stimulated production of IL-1ra by PMN, but not by MNC, of active SLE were significantly lower than that of inactive SLE or normal groups. Prednisolone (1 and 5 micrograms/ml) did not change the production of IL-1ra by normal PMN either spontaneously or LPS-stimulation in in vitro study. Moreover, the IL-1ra producing capacity of PMN in seven active SLE on admission and after intensive immunosuppressive treatment was measured. These results suggest that the defective IL-1ra production by SLE-PMN is relevant to disease activity and may be regarded as a new indicator of disease activity in patients with active SLE.

Severe infections in patients with lupus nephritis treated with immunosuppressants: A retrospective cohort study

“…3 However, patients with systemic lupus erythematosus (SLE) may have intrinsically increased risks for infections due to impaired function of polymorphonuclear neutrophils and functional hyposplaenia that may be further exacerbated by immunosuppressants. [4][5][6] Several studies have evaluated infections in SLE patients attending general rheumatology clinics or during hospitalizations [7][8][9][10][11][12][13][14][15][16] ; however, SLE patients with extra-renal manifestations have different therapeutic profiles compared to patients treated for LN. 17,18 In addition, active renal disease is also a risk factor for infection.…”

“…Hence proliferative LN is usually treated aggressively with immunosuppressive therapy, such as a combination of high dose glucocorticoids and a cytotoxic agent . However, patients with systemic lupus erythematosus (SLE) may have intrinsically increased risks for infections due to impaired function of polymorphonuclear neutrophils and functional hyposplaenia that may be further exacerbated by immunosuppressants . Several studies have evaluated infections in SLE patients attending general rheumatology clinics or during hospitalizations; however, SLE patients with extra‐renal manifestations have different therapeutic profiles compared to patients treated for LN .…”

Activation of the Nrf2/antioxidant response pathway increases IL-8 expression

“…Additionally, the endothelial isoform of IL-8 appears to have a variety of tissue-protective effects, such as mediating normal wound healing, decreasing scar formation, tissue remodeling through endothelial proliferation, myocardial protection during ischemiareperfusion injury, and maintenance of normal glomerular architecture [31][32][33][34]. Finally, neutrophils from patients with active SLE demonstrate a defect in IL-8 production that resolves with successful therapy [35]. It is thus conceivable that after acutely initiating inflammation at sites of tissue injury, which is likely beneficial, further induction of IL-8 by Nrf2 serves to attenuate neutrophil-mediated inflammation.…”

S100A8 and S100A9 inhibit neutrophil oxidative metabolismin-vitro: Involvement of adenosine metabolites

“…Reports have indicated that exaggerated or reduced rates of spontaneous neutrophil activation are linked to viral [13] or autoimmune conditions [14], implying a physiological function for spontaneous neutrophil activation. Spontaneous and stimulated activation of neutrophil oxidative metabolism has been extensively documented in-vitro [15–18].…”