Elevated interleukin-18 and skewed Th1:Th2 immune response in lupus nephritis

There is evidence that interleukin-18 plays a role in lupus nephritis (LN). Since interleukin -18 (IL-18) promotes polarization of the immune response toward Th1, we investigated level of IL-18 and assessed the phenotypic distribution of Th1 and Th2 type cells in LN. A predominance of Th1 type (IFN-gamma+) cells and significant correlations with serum IL-18 was seen in the patients with LN compared to healthy controls. Although most patients were treated with high dosage of glucocorticoid and other immunosuppressive agents, higher level of IL-18 was found in both serum and glomeruli. However, there was no paralleled upregulation of its gene expression in peripheral blood mononuclear cells. Our findings indicate that the elevated IL-18 should be a symbol of disease activity and play a major role in the pathogenesis of LN by promoting cytokine imbalance towards Th1 type immune response. We conclude that patients with LN would benefit from it while the bioactivity of this cytokine was effectively counteracted.