Th1 cytokines in the pathogenesis of lupus nephritis: the role of IL-18.
Excessive T helper cell function is a hallmark of systemic lupus erythematosus and abnormalities of T helper cytokine profiles have been implicated in loss of immune tolerance, increased antigenic load, defective B cell suppression and a variety of clinical manifestations. Here, we emphasize the importance of T helper 1-type (i.e., IFN-gamma) with respect to T helper 2-type (i.e., IL-4) cytokines in promoting the pathogenesis of lupus nephritis focusing on the critical role of IL-18, a major T helper 1 differentiation factor. IL-18 is overexpressed in patients with lupus nephritis along with higher INF-gammaand lower IL-4 production as compared to non-nephritic lupus patients. We hypothesize a pathogenic model where both the onset and aggravation of nephritis are promoted by an imbalance of immune response towards a T helper 1 cytokine predominance due to IL-18 up-regulation. In contrast, a T helper 2-skewed cytokine profile may possibly prevent the development of renal disease. In this context, IL-18 represents a novel marker of lupus nephritis and its measurement may be helpful in the assessment of patients.
Calvani
Nicola
N
DIMO, Department of Internal Medicine and Clinical Oncology, University of Bari, Piazza Giulio Ceasare 11, 70124 Bari, Italy.
Tucci
Marco
M
Richards
Hanno B
HB
Tartaglia
Paola
P
Silvestris
Franco
F
D006801:Humans; D020382:Interleukin-18 / Q000097:blood / Q000276:immunology*; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D018417:Th1 Cells / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D020382:Interleukin-18