Tumour necrosis factor-α (TNF), lymphotoxin and TNF receptor levels in serum from patients with Wegener's granulomatosis

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Abstract:

Wegener's granulomatosis (WG) is a systemic inflammatory disease with vasculitis as the key feature. Abnormal expression of tumour necrosis factor α (TNFα) is considered of prime pathogenic importance in several inflammatory diseases. The effects of TNFα are mediated by TNF receptors (TNF-R), and these receptors are often found in soluble forms (sTNF-R), which can modulate TNFα actions. To evaluate the clinical importance of the TNF family of cytokines, the serum levels of TNFα, TNFβ, now termed lymphotoxin (LTα), and sTNF-R1 and sTNF-R2 were measured by ELISA in 8 patients with WG during active disease and during immunosuppressive treatment, and in 11 healthy controls in parallel. Serum concentrations of TNFα were undetectable in all except two controls (18%) and three patients with WG (37%). After 7 days of therapy, six of the WG patients had measurable TNFα levels. Examination of the relative amounts of TNFα and sTNF-R indicated that TNFα was mostly bound to its soluble receptors. In WG, the serum levels of sTNF-R1 and sTNF-R2 were dramatically increased (p<0.01), with little or no variation during treatment. While the IL-1β levels did not deviate significantly from controls, the IL-1ra levels were significantly elevated in the WG patients throughout the study period (p<0.01).

Keywords: IL-1; Tumour necrosis factor; Wegener's granulomatosis; immunosuppressive treatment; soluble TNF receptors

Document Type: Original Article

Affiliations: 1: Institute for Inflammation Research IIR 7521 and 2: Department of Rheumatology, National University Hospital (H:S Rigshospitalet), Copenhagen, Denmark

Publication date: November 1, 2001

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