Overexpression of interleukin-12 and T helper 1 predominance in lupus nephritis.
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.
Tucci
M
M
Department of Internal Medicine and Clinical Oncology, University of Bari, Bari, Italy. m.tucci@dimo.uniba.it
Lombardi
L
L
Richards
H B
HB
Dammacco
F
F
Silvestris
F
F
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
D015415:Biomarkers; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma
J Exp Med. 1984 Jul 1;160(1):310-6
6429267
Clin Exp Immunol. 2002 Nov;130(2):345-51
12390326
J Immunol. 1999 Dec 15;163(12):6884-91
10586090
J Exp Med. 2005 Jan 17;201(2):233-40
15657292
Arthritis Rheum. 2001 Sep;44(9):2097-106
11592372
J Am Soc Nephrol. 2004 Feb;15(2):241-50
14747370
Arthritis Rheum. 2003 May;48(5):1326-31
12746905
Clin Nephrol. 1993 Jul;40(1):16-21
8358870
Lupus. 2000;9(8):589-93
11035433
J Immunol. 1997 Jun 1;158(11):5484-91
9164971
J Am Soc Nephrol. 2001 Jul;12(7):1369-1382
11423566
Kidney Int. 2001 Dec;60(6):2173-80
11737591
Cytokine. 1999 Oct;11(10):805-11
10525320
Oncogene. 1996 Nov 21;13(10):2281-5
8950996
Medicine (Baltimore). 1978 Sep;57(5):371-410
682942
Scand J Rheumatol. 1998;27(3):219-24
9645418
J Clin Invest. 1996 Apr 1;97(7):1597-604
8601623
J Immunol. 2003 Apr 1;170(7):3915-25
12646661
Arthritis Rheum. 2004 Jun;50(6):1842-9
15188361
J Immunol. 1997 May 1;158(9):4381-8
9127002
J Exp Med. 1989 Sep 1;170(3):827-45
2504877
J Leukoc Biol. 2000 Oct;68(4):495-502
11037970
Nephron. 1997;76(4):425-33
9274840
Semin Nephrol. 1999 Jan;19(1):57-66
9952281
Proc Soc Exp Biol Med. 1998 Dec;219(3):171-82
9824540
Rheumatology (Oxford). 2003 Aug;42(8):935-8
12730502
Transplantation. 1991 Jul;52(1):58-63
1858155
Kidney Int. 2003 Sep;64(3):897-905
12911539
Clin Exp Immunol. 2004 Oct;138(1):171-8
15373921
Cytokine. 1998 Feb;10(2):140-7
9512904
Arthritis Rheum. 1997 Sep;40(9):1725
9324032
Clin Exp Immunol. 1999 Apr;116(1):169-73
10209522
Arthritis Rheum. 1982 Nov;25(11):1271-7
7138600
Lupus. 2002;11(6):384-7
12139377
Arthritis Rheum. 1996 Mar;39(3):379-85
8607886
Cytokine. 1998 Feb;10(2):148-53
9512905
Arthritis Rheum. 1998 May;41(5):838-44
9588735
J Immunol. 1998 Jul 1;161(1):494-503
9647261
Autoimmun Rev. 2004 Feb;3(2):7-11
15003182
Am J Kidney Dis. 1994 Feb;23(2):242-6
8311082
Arthritis Rheum. 1999 Aug;42(8):1644-8
10446863