title: Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus.
abstract: Cytokines are believed to play an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, for tumour necrosis factor alpha (TNF-alpha) both beneficial and deleterious effects have been reported. To obtain information about the involvement of this cytokine in the pathophysiology of SLE, serum levels of TNF-alpha, the soluble forms of the 55 and 75 kDa tumour necrosis factor receptors (TNF-R55 and TNF-R75), and interleukin-6 (IL-6) were measured by ELISA in nine female patients over a period of 2 yr. Compared to healthy controls, levels of TNF-alpha (median 47 pg/ml, range < 15-222 pg/ml), TNF-R55 (median 1.9 ng/ml, range 0.8-10.8 ng/ml), TNF-R75 (median 4.7 ng/ml, range 1.5-15 ng/ml) and IL-6 (median 3.5 pg/ml, range < 3.5-52 pg/ml) were significantly elevated in SLE patients (P < 0.0001 vs controls in all cases). There were strong correlations between TNF-alpha and its soluble receptors (P < 0.0001). Moreover, TNF-alpha and both TNF-Rs strongly correlated with clinical and serological parameters of disease activity, such as the European Consensus Lupus Activity Measurement (ECLAM) score, anti-dsDNA antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anaemia (P < 0.0001 for all comparisons). TNF-alpha and TNF-R75 also correlated with IL-6 (P < 0.0001). However, no correlation between IL-6 and ECLAM was found, and the correlation of IL-6 with anti-dsDNA was relatively weak; in contrast, IL-6 correlated strongly with CRP and ESR (P < 0.0001). Although these data do not allow us ultimately to discriminate between beneficial and deleterious effects of TNF-alpha, they nevertheless suggest a central role for the TNF system in the pathophysiology of SLE.
authors.affiliation: 2nd Department of Medicine, Lainz Hospital, Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Studnicka-Benke
authors.forename: G
authors.initials: G
authors.lastname: Steiner
authors.forename: P
authors.initials: P
authors.lastname: Petera
authors.forename: J S
authors.initials: JS
authors.lastname: Smolen
mesh_terms: D000328:Adult; D000368:Aged; D015551:Autoimmunity; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000502:physiology*; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha