Up-regulation of IL-18 and predominance of a Th1 immune response is a hallmark of lupus nephritis.
There is evidence that nephritis is dominated by a Th1 immune response in systemic lupus erythematosus. Since IL-18 promotes polarization of the immune response toward Th1, we investigated the role of this cytokine in lupus nephritis (LN). A total of 133 lupus patients and 44 healthy subjects were enrolled. Demographic and clinical characteristics with renal biopsy data were recorded. IL-18 along with IFN-gamma and IL-4, two prototypical of Th1 and Th2 cytokines, were measured in serum by ELISA. Peripheral blood lymphocytes were analysed by flow cytometry for IFN-gamma and IL-4. IL-18 expression was determined by immunohistochemistry in 13 renal biopsy specimens from patients with LN and 2 controls. Serum IL-18 was higher in lupus patients than in controls. Levels of IL-18 correlated with urinary microalbumin and were increased in patients with LN when compared to those without LN. IL-18 expression was also increased within the glomeruli of nephritic patients and was primarily detected within the mesangial matrix and in infiltrating mononuclear cells. Measurement of IFN-gamma and IL-4 in either sera or peripheral blood lymphocytes showed high IFN-gamma along with low IL-4 expression in LN patients compared to patients without nephritis. A positive correlation between serum IL-18 and IFN-gamma levels was found. IL-18 may play a prominent role in the pathogenesis of LN by promoting a cytokine imbalance towards a Th1 immune response. Measurement of IL-18 may be helpful for the early identification of lupus patients with LN and may help gauge the response to treatment in patients with active LN undergoing treatment.
Calvani
N
N
Department of Internal Medicine and Clinical Oncology, University of Bari, Italy.
Richards
H B
HB
Tucci
M
M
Pannarale
G
G
Silvestris
F
F
D000328:Adult; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D020382:Interleukin-18 / Q000097:blood / Q000276:immunology*; D015847:Interleukin-4 / Q000097:blood / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology; D008297:Male; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D020382:Interleukin-18; D015847:Interleukin-4; D007371:Interferon-gamma