Serum IL-6, TNFα, p55 srTNFα, p75 srTNFα, srIL-2α Levels and Disease Acitivity in Systemic Lupus Erythematosus

Abstract

The aim of this study was to determine whether the levels of serum cytokines IL-6 and TNFalpha and of the soluble receptors p55 srTNFalpha, p75 srTNFalpha and srIL-2ac are valuable markers of disease activity in patients with systemic lupus erythematosus (SLE) compared with the established parameters of anti-dsDNA, C3, C4 and CH50. Forty patients with SLE, 19 ambulatory and 21 hospitalised, were included in this study. On the day of blood sampling a clinical examination was performed and SLEDAI and ECLAM disease activity scores were used to assess disease activity. Nineteen patients had inactive disease and 21 patients had active disease. Thirteen patients from the second group developed nephritis. In these patients the blood sampling and disease activity assessment were performed twice (at presentation and 6 months after treatment). Serum levels of cytokines and soluble receptors were measured by ELISA. Serum levels of cytokines and soluble receptors of patients with active disease were significantly higher than in patients with inactive disease (IL-6 p = 0.0004, TNFalpha p = 0.0015, srIL-2c p<0.0001, p55 srTNFalpha p<0.0001, p75 srTNFalpha p<0.0001). Serum soluble receptor levels of patients with inactive disease were higher than those of healthy controls (p55 srTNFalpha p<0.0001, p75 srTNFalpha p = 0.0002, srIL-2alpha p = 0.0012). No significant difference was found for TNFalpha and IL-6 (TNFalpha p=0.015, IL-6 p=0.019). Serum TNFalpha levels and especially srIL-2alpha, p55 srTNFalpha( and p75 srTNFalpha levels correlated strongly with SLEDAI and ECLAM disease activity scores, anti-dsDNA, C3, C4 and CH50 (p<0.0001). Serum soluble receptor (srIL-2alphac, p55 srTNFa, p75 srTNFalpha) levels were higher in patients with nephritis before treatment and decreased significantly 6 months after treatment (p=0.005). The same trend was noticed with SLEDAI and ECLAM disease activity scores (p = 0.005) and anti-dsDNA (p = 0.008). In contrast, no significant differences were observed for C3 and C4 levels before and after treatment, which suggests that soluble receptors of cytokines are more sensitive markers of disease activity than C3 or C4 in predicting improvement. Serum levels of srIL-2alpha, p55 srTNFalpha and p75 srTNFalpha could provide useful information about disease activity in SLE patients, especially in cases where the other markers do not.

Increased level of tumor necrosis factor-α in patients with antiphospholipid syndrome: marker not only of inflammation but also of the prothrombotic state

“…In SLE group of patients, elevation of both markers and their association with disease activity has already been shown [11,12,14,15,23]. We support these findings by showing that patients with an active disease (decreased C4 levels, presence of ds-DNA autoantibodies and renal involvement) had significantly higher levels of TNF-a and sIL-2R than the others.…”

Excreted urinary mediators in an animal model of experimental immune nephritis with potential pathogenic significance

“…Interestingly, the expression of TNFRII (but not TNFRI) on intrinsic renal cells has recently been shown to be important in experimental immune nephritis (38). Additionally, levels of serum TNFRI have been noted to be increased in human systemic lupus erythematosus (17,18). There is a single report of hyperexpression of TNFRI in the kidneys of patients with proliferative lupus nephritis (19), but TNFRI has not yet been examined in the urine of patients with lupus or immune nephritis.…”

“…Finally, we sought to determine the pathophysiologic relevance of these 4 molecules in immune nephritis. Some information is already available concerning the role of VCAM-1, P-selectin, and TNFRI in renal disease (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19), as discussed below. However, much less is known about the role of CXCL16, which is a chemokine expressed on dendritic cells and macrophages.…”

The pathophysiology of photosensitivity in lupus erythematosus

“…Raised circulating levels of TNF-a may correlate with disease activity in human systemic lupus (201). A polymorphic variant in the TNF-a promoter in humans (TNF-a 308A) is associated with increased production of TNF-a (277).…”