Up-regulation of IL-18 and predominance of a Th1 immune response is a hallmark of lupus nephritis

Author:

CALVANI N1,RICHARDS H B2,TUCCI M1,PANNARALE G3,SILVESTRIS F1

Affiliation:

1. Department of Internal Medicine and Clinical Oncology

2. Department of Medicine, Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville, USA

3. Department of Internal and Public Medicine, Division of Nephrology, University of Bari, Italy

Abstract

SUMMARY 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-γ 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-γ 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-γ and IL-4 in either sera or peripheral blood lymphocytes showed high IFN-γ along with low IL-4 expression in LN patients compared to patients without nephritis. A positive correlation between serum IL-18 and IFN-γ 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.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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