Dysregulation of IL-6 production has been proposed as a pathogenic mechanism in SLE. We asked if serum or urine IL-6 levels could serve as indicators of systemic lupus erythematosus (SLE) disease activity. Using a sensitive enzyme-linked immunosorbent assay (ELISA), we measured serum and urine IL-6 in 56 SLE patients. Disease activity was assessed using a standard clinical index, the Systemic Lupus Activity Measure (SLAM). Only seven of 56 SLE patients had elevated serum IL-6 levels, compared with 1 of 32 controls (NS). SLE disease activity did not correlate with serum IL-6 levels. Sixteen of 50 SLE patients in whom urine IL-6 was measured exhibited elevated urine IL-6 levels, compared with 1 of 17 controls (p = < 0.05). Urine IL-6 levels correlated with overall disease activity and with the presence of active urinary sediment. Our results indicate that serum IL-6 is not a predictor of disease activity in SLE, but that urine IL-6 may be a marker of active nephritis.
Balow J.Lupus nephritis. Ann Int Med1987; 106: 79-94.
2.
Koffler D., Schur PH, Kunkel HGImmunological studies concerning the nephritis of systemic lupus erythematosus . J Exp Med1967; 126: 607-624.
3.
Kishimoto T. , Hirano T.Molecular regulation of the B lymphocytes response. Annual Rev Immunol1988; 6: 485-512.
4.
Heinrich PC, Castell JV, Andus T.Interleukin-6 and the acute phase response. Biochem J1990; 265: 621-636.
5.
Kitani M. et al. Autostimulatory effects of IL-6 on excessive B cell differentiation in patients with systemic lupus erythematosus: analysis of IL-6 production and IL-6R expression. Clin Exp Immunol1992 ; 88: 75-83.
6.
Blaese RM, Grayson J., Steinberg ADIncreased Ig-secreting cells in the blood of patients with active SLE. Am J Med1980; 69: 345-350.
7.
Klashman DJ, Martin RA, Martinez-Maza O., Stevens RHIn vitro regulation of B cell differentiation by interleukin-6 and soluble CD23 in systemic lupus erythematosus B cell subpopulations and antigen-induced normal B cells. Arthritis Rheum1991; 34: 276-285.
8.
Pelton BK, Hylton W., Denham A.Activation of IL-6 production by UV irradiation of blood mononuclear cells from patients with systemic lupus erythematosus. Clin Exp Immunol1992; 89: 251-254.
9.
Breen EC et al. Infection with HIV is associated with elevated IL-6 levels and production. J Immunol1990; 144: 480-484.
10.
Deviere J. et al. High interleukin-6 serum levels and increased production by leukocytes in alcoholic liver cirrhosis: correlation with IgA serum levels and lymphokine production. Clin Exp Immunol1989; 77: 221-225.
11.
Gueme PA et al. Synovium as a source of interleukin-6 in vitro: contribution to local and systemic manifestations of arthritis. J Clin Invest1989; 83: 585.
12.
Linker-Israeli M. et al. Elevated levels of endogenous IL-6 in systemic lupus erythematosus. J Immunol1991; 147: 117-123.
13.
Iwano M. et al. Urinary levels of IL-6 in patients with active lupus nephritis . Clin Nephrol1993; 40 (1): 16-21.
14.
Tan EM et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum1982; 25: 1271-1277.
15.
Liang MH, Socher SA, Larson MG, Schur PHReliability and validity of six systems for the clinical assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum1989; 32: 1107-1118.
16.
Emlen W., Jarusiripipat P., Burdick G.A new double-stranded DNA specific ELISA for the detection of DNA antibodies . J Immunol Methods1990; 132: 91-101.
17.
Metsarinne KP et al. Plasma interleukin-6 and renin substrate in reactive arthritis, rheumatoid arthritis, and systemic lupus erythematosus . Rheumatol Int1992; 12: 93-96.
18.
Swaak Ajg, van Rooyen A., Aarden L.Interleukin-6 (IL-6) and acute phase proteins in the disease course of patients with systemic lupus erythematosus. Rheumatol Int1989; 8: 263-268.
19.
Spronk PE, ter Borg J., Limburg P., Kallenberg C.Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity? Clin Exp Immunol1992 ; 90: 106-110.
20.
ter Borg EJ et al. C-reactive protein levels during disease exacerbations and infections in systemic lupus erythematosus: A prospective longitudinal study. J Rheumatol1990; 17: 1642-1648.
21.
Gaillard J-P. et al. Increased and highly stable levels of functional soluble interleukin-6 receptor in sera of patients with monoclonal gammopathy. Eur J Immunol1993; 23: 820-824.
22.
Cytokine Bulletin, R&D Systems; Spring 1994.
23.
May LT et al. High levels of 'complexed' interleukin-6 in human blood. J Biological Chem1992; 267: 19698-19704.
24.
Bendtzen K. et al. Autoantibodies to cytokines-friends or foes? Immunol Today11: 167-169.
25.
Alcocer-Verela JD, Aleman-Hoey D., Alarcon-Segovia D.Interleukin-1 and interleukin-6 activities are increased in the cerebrospinal fluid of patients with CNS lupus erythematosus and correlate with local late T-cell activation markers. Lupus1992; 1: 111-117.
26.
Tsai C-Y. et al. Cerebrospinal fluid interleukin-6, prostaglandin E2, and autoantibodies in patients with neuropsychiatric systemic lupus erythematosus and central nervous system infections. Scand J Rheumatol1994; 23: 57-63.
27.
Hirohata S. , Miyamoto T.Elevated levels of interleukin-6 in cerebrospinal fluid from patients with systemic lupus erythematosus and central nervous system involvement. Arthritis Rheum1990; 33: 644-649.
28.
Tomino et al. Urinary levels of interleukin-6 and disease activity in patients with IgA nephropathy. Am J Nephrol1991; 11: 459-464.
29.
Dohi K. et al. The prognostic significance of urinary interleukin 6 in IgA nephropathy. Clin Nephrol1991; 35: 1-5.
30.
Chen W., Lin C-Y.Augmented expression of interleukin-6 and interleukin-1 genes in the mesangium of IgM mesangial nephropathy. Nephron1994 ; 68: 10-19.
31.
Horii Y. et al. Involvement of IL-6 in mesangial proliferative glomerulonephritis . J Immunol1989; 143: 3949-3955.
32.
VanOers MHJ, Van der Heyden AAPAM, Aarden LA. Interleukin 6 (IL-6) in serum and urine of renal transplant recipients. Clin Exp Immunol1988; 71: 314-319.
33.
Jacobson SH , Hylander B., Wretlind B., Brauner A.Interleukin-6 and interleukin-8 in serum and urine in patients with acute pyelonephritis in relation to bacterial-virulence-associated traits and renal function. Nephron1994; 67: 172-179.
34.
Fukatsu A. et al. Distribution of interleukin-6 in normal and diseased human kidney . Laboratory Invest1991; 65: 61-66.
