title: Overexpression of interleukin-12 and T helper 1 predominance in lupus nephritis.
abstract: Imbalance of cytokine homeostasis is a prominent feature of both experimental and human systemic lupus erythematosus (SLE). Because interleukin (IL)-12 promotes interferon (IFN)-gamma production leading to polarization of peripheral cells toward a T helper (Th) 1 phenotype, we investigated its role in lupus nephritis (LN). Soluble Th1 and Th2 cytokines were measured by enzyme-linked immunosorbent assay (ELISA) in sera and urines of SLE patients and controls. Th1/Th2 peripheral lymphocyte polarization was determined by flow cytometry. Glomerular accumulation of IL-12 was evaluated by immunohistochemistry, whereas urinary IL-12 was evaluated by ELISA. Higher serum IL-12 levels in SLE were associated with LN, whereas IL-4 was unrelated to the renal damage. Peripheral cells from LN patients showed a Th1 phenotype with a high IFN-gamma expression that paralleled the severity of renal damage. IL-12 was present within glomerular mononuclear cells in classes IV and V LN, and its accumulation was correlated strongly with urinary levels. IL-12 overexpression in SLE may contribute to the development of LN. Both serum and urinary IL-12 elevation reflect its glomerular production and parallel Th1 polarization of peripheral T cells and high IFN-gamma production. In SLE patients, IL-12 measurement may thus be predictive of the development of LN.
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari, Bari, Italy. m.tucci@dimo.uniba.it
authors.forename: M
authors.initials: M
authors.lastname: Tucci
authors.forename: L
authors.initials: L
authors.lastname: Lombardi
authors.forename: H B
authors.initials: HB
authors.lastname: Richards
authors.forename: F
authors.initials: F
authors.lastname: Dammacco
authors.forename: F
authors.initials: F
authors.lastname: Silvestris
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood / Q000378:metabolism* / Q000652:urine; D015847:Interleukin-4 / Q000097:blood; D007678:Kidney Glomerulus / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008181:Lupus Nephritis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015415:Biomarkers; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma
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