Abstract
Henoch-Schönlein purpura (HSP) is one of the most common types of vasculitis disorders in childhood and is characterized by a rash, arthritis, abdominal pain, and renal involvement. The factors that determine and mediate the severity of HSP and its renal involvement remain poorly understood, although it is likely that pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), are involved in the pathogenesis. Serum and urine levels of TNF-α were measured in children with HSP in the acute and convalescent phases by ELISA. Serum TNF-α levels were significantly higher in proteinuric HSP in the acute phase (36.6±8.5 pg/ml) compared with those with HSP without renal involvement and those with hematuric HSP (25.4±4.5 and 27.1±3.9 pg/ml) (P<0.005). However, these significantly higher levels disappeared in the convalescent phase. Using matched serum samples from the same patients, serum TNF-α levels of proteinuric HSP patients were significantly lower in the convalescent phase (29.9±4.6 pg/ml, P <0.05) than in the acute phase (39.1±8.2 pg/ml). Although urine TNF-α levels were higher in proteinuric HSP in the acute phase and reduced in the convalescent phase, there were no significantly high or low levels. These results suggest that increased TNF-α levels in the serum induce a series of functional and morphological changes in the glomerular cells in the acute phase and may be used as markers for monitoring the disease activity of HSP with severe renal involvement.
Similar content being viewed by others
References
Cassidy JT, Petty RE (1995) Vasculitis, Henoch-Schönlein purpura. In: Cassidy JT, Petty E (eds) Pediatric rheumatology, 3rd edn. Saunders, Philadelphia, pp 384–388
Haycock GB (1998) The nephritis of Henoch-Schönlein purpura. In: Davidson AM, Cameron JS, Grünfeld JP, Kerr D, Ritz E (eds) Oxford textbook of clinical nephrology, 2nd edn. Oxford Medical Publications, New York, pp 845–917
Takemura T, Yoshioka K, Murakami K, Akano N, Okada M, Aya N, Maki S (1994) Cellular localization of inflammatory cytokines in human glomerulonephritis. Virchows Arch 424:459–464
Ozenn S, Saatcii U, Tinaztepee K, Bakkalogluu A, Barutt A (1994) Urinary tumor necrosis factor levels in primary glomerulopathies. Nephron 66:291–294
Noronhaa IL, Kruger C, Andrassyy K, Ritz E, Waldherrr R (1993) In situ production of TNF-alpha, IL-1 beta and IL-2R in ANCA-positive glomerulonephritis. Kidney Int 43:682–692
Bertanii T, Abbate M, Zojaa C, Corna D, Perico N, Ghezzi P, Remuzzi G (1989) Tumor necrosis factor induces glomerular damage in the rabbit. Am J Pathol 134:419–430
Besbas N, Saatci U, Ruacan S, Ozen S, Sungur A, Bakkaloglu A, Elnahas AM (1997) The role of cytokines in Henoch Schönlein purpura. Scand J Rheumatol 26:456–460
Wu TH, Wu SC, Huang TP, Yu CL, Tsai CY (1996) Increased excretion of tumor necrosis factor alpha and interleukin 1 beta in urine from patients with IgA nephropathy and Schönlein-Henoch purpura. Nephron 74:79–88
Gattorno M, Vignola S, Barbano G, Sormani MP, Sabatini F, Buoncompagni A, Picco P, Pistoia V (2000) Tumor necrosis factor induced adhesion molecule serum concentrations in Henoch-Schönlein purpura and pediatric systemic lupus erythematosus. J Rheumatol 27:2251–2255
Mills JA, Michel BA, Bloch DA, Calabrese LH, Hunder GG, Arend WP, Edworthy SM, Fauci AS, Leavitt RY, Lie JT (1990) The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura. Arthritis Rheum 33:1114–1121
Knight JF (1990) The rheumatic poison: a survey of some published investigations of the immunopathogenesis of Henoch-Schönlein purpura. Pediatr Nephrol 4:533–541
Bradley JR, Lockwood CM, Thiru S (1994) Endothelial cell activation in patients with systemic vasculitis. Q J Med 87:741–745
Carlos TM, Harlan JM (1994) Leucocyte-endothelial adhesion molecules. Blood 84:2068–2070
Rostoker G, Rymer JC, Bagnard G, Petit-Phar M, Griuncelli M, Pilatte Y (1998) Imbalances in serum proinflammatory cytokines and their soluble receptors: a putative role in the progression of idiopathic IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis, and a potential target of immunoglobulin therapy? Clin Exp Immunol 114:468–476
Leeuwenberg JF, Van Damme J, Meager T, Jeunhomme TM, Buurman WA (1988) Effects of tumor necrosis factor on the interferon-gamma induced major histocompatibility complex class II antigen expression by human endothelial cells. Eur J Immunol 18:1469–1472
Cavender DE, Edelbaum D, Ziff M (1989) Endothelial cell activation induced by tumor necrosis factor and lymphotoxin. Am J Pathol 134:551–560
Nawroth PP, Bank I, Handley D, Cassimeris J, Chess L, Stern D (1986) Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med 163:1363–1375
Radeke HH, Meier B, Topley N, Floge J, Habermehl GG, Resch K (1990) Interleukin-1 alpha and tumor necrosis factor alpha induce oxygen radical production in mesangial cells. Kidney Int 37:767–775
Furukawa S, Matsubara T, Yone K, Hirano Y, Okunura K, Yabuta K (1992) Kawasaki disease differs from anaphylactoid purpura and measles with regard to tumor necrosis factor and interleukin 6 in serum. Eur J Pediatr 151:44–47
Tomosugi NI, Cashman SJ, Hay H, Pusey CD, Evans DJ, Shaw A, Rees AJ (1989) Modulation of antibody-mediated glomerular injury in vivo by bacterial lipopolysaccharide, tumor necrosis factor, and IL-1. J Immunol 142:3083–3090
Royall JA, Berkow RL, Beckman JS, Cunningham MK, Matalon S, Freeman BA (1989) Tumor necrosis factor and interleukin 1 alpha increase vascular endothelial permeability. Am J Physiol 257:399–410
Magil AB (1995) Tubulointerstitial lesions in human membranous glomerulonephritis: relationship to proteinuria. Am J Kidney Dis 25:375–379
D’Amico G (1998). Tubulo-interstitial damage in glomerular disease: its role in the progression of the renal damage. Nephrol Dial Transplant 13:S80–S85
Acknowledgements
This study was partly supported by a grant from Korean Ministry of Health and Welfare (HMP-98-M-5–0053) and Korea Science and Engineering Foundation (KOSEF, R01–2002–000–00251–0). The author thanks Dr. D-H Jeong and Y-J Song for their technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ha, TS. The role of tumor necrosis factor-α in Henoch-Schönlein purpura. Pediatr Nephrol 20, 149–153 (2005). https://doi.org/10.1007/s00467-004-1726-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-004-1726-3