Top

Published in:

01-04-2006 | Original Article

Daily urinary interleukin-11 excretion correlated with proteinuria in IgA nephropathy and lupus nephritis

Authors: Jien-Wen Chien, Woan-Ling Chen, Yi-Giien Tsui, Min-Chun Lee, An-Yi Lin, Ching-Yuang Lin

Published in: Pediatric Nephrology | Issue 4/2006

Abstract

Interleukin-11 (IL-11) is a multifunctional cytokine with both thrombopoietic and anti-inflammatory effects. In an animal study IL-11 was shown to reduce proteinuria in mice with necrotizing glomerulonephritis. The purpose of this current study is to explore the role of IL-11 in human glomerulonephritis. Subjects of this study were patients with proteinuria (daily urine protein excretion >40 mg/m² per hour) and underlying pathology of IgA nephropathy (IgAN) (n=20), lupus nephritis (LN) (n=40), and idiopathic nephrotic syndrome (INS) (n=68). Daily urinary IL-11 level was measured by enzyme-linked immunosorbent assay (ELISA). Correlation between urinary IL-11 and urinary protein was determined by Pearson’s correlation coefficient. Another five patients with serial data of urinary protein, IL-11 and IL-11 messenger RNA (mRNA) expression in urine sediment are presented. The correlation between urinary IL-11 and daily urinary protein was significant for patients with IgAN (r=0.596, P=0.006) and LN (r=0.630, P<0.001), but not for patients with INS (r=0.030, P=0.812). Serial data revealed the same correlation. Furthermore, the peak of urinary IL-11 mRNA preceded that of urinary IL-11. We conclude that daily urinary IL-11 excretion is correlated with urinary protein loss in nephritis having local T helper (Th)1 predominant immune response, such as IgAN and LN. Local IL-11 production may serve as a counter cytokine against Th1-mediated inflammation.

Mellors RC (1955) Histochemical demonstration of the in vivo localization of antibodies, antigenic components of the kidney and the pathogenesis of glomerulonephritis. J Histochem Cytochem 3:284PubMed

Holdsworth SR, Kitching AR, Tipping PG (1999) Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in glomerulonephritis. Kidney Int 55:1198–1216CrossRefPubMed

Kang J, Bai KM, Wang BL, Yao Z, Pang XW, Chen WF (1994) Increased production of interleukin 4 in children with simple idiopathic nephritic syndrome. Chin Med J (Engl) 107:347–350

Yano N, Endoh M, Nomoto Y, Sakai H, Fadden K, Rifai A (1997) Phenotypic characterization of cytokine expression in patients with IgA nephropathy. J Clin Immunol 17:396–403CrossRefPubMed

Chien JW, Lin CY (2003) Autoantibodies to dsDNA, Ro/SSA, and La/SSB in systemic lupus erythematosus. Adv Clin Chem 37:129–172PubMed

Chien JW, Lin CY, Yang LY (2001) Correlation between anti-Ro/La titers and clinical findings of patients with systemic lupus erythematosus. Chin Med J 64:283–291

Segal R, Bermas BL, Dayan M, Kalush F, Shearer GM, Mozes E (1997) Kinetics of cytokine production in experimental systemic lupus erythematosus. J Immunol 158:3009–3016PubMed

Viallard JF, Pellegrin JL, Ranchin V, Schaeverbeke T, Dehais J, Longy-Boursier M, Ragnaud JM, Leng B, Moreau JF (1999) Th1 (IL-2, interferon-gamma (IFN-γ)) and Th2 (IL-10, IL-4) cytokine production by peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 115:189–195CrossRefPubMed

Schwertschlag US, Trepicchio WL, Dykstra KH, Keith JC, Turner KJ, Dorner AJ (1999) Hematopoietic, immunomodulatory and epithelial effects of interleukin-11. Leukemia 13:1307–1315CrossRefPubMed

10.

Trepicchio WI, Wang L, Bozza M, Dorner AJ (1997) IL-11 regulates macrophage effector function through the inhibition of nuclear factor-kappa B. J Immunol 159:5661–5670PubMed

11.

Antonio C, Marina R, Silvia C, Giampiero G, Francesca R, Pierluigi T, Michela S, Alexis G, Miriam F, Sante T, Roberto ML (2001) Interleukin-11 induces Th2 polarization of human CD4+ cells. Blood 97:2758–2763CrossRefPubMed

12.

Moreland L, Gugliotti R, King K, Chase W, Weisman M, Greco T, Fife R, Korn J, Simms R, Tesser J, Hillson J, Caldwell J, Schnitzer T, Lyons D, Schwertschlag U (2001) Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis. Arthritis Res 3:247–252CrossRefPubMed

13.

Minshall E, Chakir J, Laviolette M, Molet S, Zhu Z, Olivenstein R, Elias JA, Hamid Q (2000) IL-11 expression is increased in severe asthma: association with epithelial cells and eosinophils. J Allergy Clin Immunol 105:232–238CrossRefPubMed

14.

Zheng T, Zhu Z, Wang J, Homer RJ, Elias JA (2001) IL-11: insights in asthma from overexpression transgenic modeling. J Allergy Clin Immunol 108:489–496CrossRefPubMed

15.

Lai PC, Cook T, Smith J, Keith JC Jr, Pusey CD, Tam FWK (2001) Interleukin-11 attenuates nephrotoxic nephritis in Wistar Kyoto rats. J Am Soc Nephrol 12:2310–2320PubMed

16.

Churg J, Sobin H (1982) WHO monograph: renal disease. Classification and atlas of glomerular disease. Igaku-Soin, Tokyo

17.

Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ (1982) Special article: the 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMedCrossRef

18.

Zappitelli M, Duffy C, Bernard C, Scuccimarri R, Watanabe Duffy K, Kagan R, Gupta IR (2004) Clinicopathological study of the WHO classification lupus nephritis. Pediatr Nephrol 19:503–510CrossRefPubMed

19.

Li B, Hartono C, Ding R, Sharma VK, Ramaswamy R, Qian B, Serur D, Mouradian J, Schwartz JE, Suthanthiran M (2001) Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine. N Engl J Med 344:947–954CrossRefPubMed

20.

Paul SR, Bennett F, Calvetti JA, Kelleher K, Wood CR, O’Hara RM Jr, Leary AC, Sibley B, Clark SC, Williams DA, Yang Y-C (1990) Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci U S A 87:7512–7516PubMedCrossRef

21.

Davidson AJ, Freeman SA, Crosier KE, Wood CR, Crosier PS (1997) Expression of murine interleukin 11 and its receptor alpha-chain in adult and embryonic tissues. Stem Cells 15:119–124PubMedCrossRef

22.

Wang Y, Rangan GK, Tay YC, Wang Y, Harris DCH (1999) Induction of monocyte chemoattractant protein-1 by albumin is mediated by nuclear factor κB in proximal tubule cells. J Am Soc Nephrol 10:1204–1213PubMed

23.

Tepler I, Elias L, Smith JW II, Hussein M, Rosen G, Chang AY-C, Moore JO, Gordon MS, Kuca B, Beach KJ, Loewy JW, Garnick MB, Kaye JA (1996) A randomised placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy. Blood 87:3607–3614PubMed

24.

Harper SJ, Pringle JH, Wicks AC, Hattersley J, Layward L, Allen A, Gillies A, Lauder I, Feehally J (1994) Expression of J chain mRNA in duodenal IgA plasma cells in IgA nephropathy. Kidney Int 45:836–844PubMedCrossRef

25.

Layward L, Allen AC, Hattersley JM, Harper SJ, Feehally J (1993) Elevation of IgA in IgA nephropathy is localized in the serum and not saliva and is restricted to the IgA1 subclass. Nephrol Dial Transplant 8:25–28PubMed

26.

Jennette JC, Wieslander J, Tuttle R, Falk RJ (1991) Serum IgA-fibronectin aggregates in patients with IgA nephropathy and Henoch–Schonlein purpura: diagnostic value and pathogenic implications. Am J Kidney Dis 18:466–471PubMed

27.

Aucouturier P, Monteiro RC, Noel LH, Preud’homme JL, Lesavre P (1989) Glomerular and serum immunoglobulin G subclasses in IgA nephropathy. Clin Immunol Immunopathol 51:338–347CrossRefPubMed

28.

Roberts JL, Wyatt RJ, Schwartz MM, Lewis EJ (1983) Differential characteristics of immune-bound antibodies in diffuse proliferative and membranous forms of lupus glomerulonephritis. Clin Immunol Immunopathol 29:223–241CrossRefPubMed

29.

Chan RW, Tam LS, Li EK, Lai FM, Chow KM, Lai KB, Li PK, Szeto CC (2003) Inflammatory cytokine gene expression in the urinary sediment of patients with lupus nephritis. Arthritis Rheum 48:1326–1331CrossRefPubMed

30.

Assadi FK (2005) Value of urinary excretion of microalbumin in predicting glomerular lesions in children with isolated microscopic hematuria. Pediatr Nephrol 20:1131–1135CrossRefPubMed

31.

Park YH, Choi JY, Chung HS, Koo JW, Kim SY, Namgoong MK, Park YS, Yoo KH, Lee KY, Lee DY, Lee SJ, Lee JE, Chung WY, Hah TS, Cheong HI, Choi Y, Lee KS (2005) Hematuria and proteinuria in a mass school urine screening test. Pediatr Nephrol 20:1126–1130CrossRefPubMed

32.

Aoyama K, Uchida T, Takanuki F, Usui T, Watanabe T, Higuchi S, Toyoki T, Mizoguchi H (1997) Pharmacokinetics of recombinant human interleukin-11 (rhIL-11) in healthy male subjects. Br J Clin Pharmacol 43:571–578PubMedCrossRef

33.

Fiorito S, Magrini L, Goalard C (2003) Pro-inflammatory and anti-inflammatory circulating cytokines and periprosthetic osteolysis. J Bone Joint Surg Br 85:1202–1206CrossRefPubMed

34.

Takagi A, Yabe Y, Oka Y, Sawai K, Takakura Y, Hashida M (1997) Renal disposition of recombinant human interleukin-11 in the isolated perfused rat kidney. Pharmaceutical Res 14:86–90CrossRef

Title: Daily urinary interleukin-11 excretion correlated with proteinuria in IgA nephropathy and lupus nephritis
Authors: Jien-Wen Chien
Woan-Ling Chen
Yi-Giien Tsui
Min-Chun Lee
An-Yi Lin
Ching-Yuang Lin
Publication date: 01-04-2006
Publisher: Springer-Verlag
Published in: Pediatric Nephrology / Issue 4/2006
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-006-0016-7

At a glance: The STEP trials

Springer Medicine

Daily urinary interleukin-11 excretion correlated with proteinuria in IgA nephropathy and lupus nephritis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2006

Long-term renal function in heart transplant children on cyclosporine treatment

Glutathione depletion and increased apoptosis rate in human cystinotic proximal tubular cells

Hyperkalemic distal renal tubular acidosis associated with Rett syndrome

Gender and vesico-ureteral reflux: a multivariate analysis

Clinical course of 110 children and adolescents with primary focal segmental glomerulosclerosis

Nondiabetic consequences of obesity on kidney