Wegeners granulomatosis (WG) is a systemic inflammatory disease with vasculitis as a key feature. Abnormal expression of tumour necrosis factor a (TNFa) is considered of prime pathogenic importance in several inflammatory diseases. The effects of TNFa are mediated by TNF receptors (TNF-R), and these receptors are often found in soluble forms (sTNF-R), which can modulate TNFa actions. To evaluate the clinical importance of the TNF family of cytokines, the serum levels of TNFa, TNFb, now termed lymphotoxin (LTa), 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. were measured in parallel by ELISA. Serum concentrations of TNFa were undetectable in all except 2 controls (18 %) and 3 (37 %) patients with WG. After 7 days of therapy, 6 of the WG patients had measurable TNFa levels. Examination of the relative amounts of TNFa and sTNF-R indicated that TNFa was mostly bound to its soluble receptors. In WG, the serum levels of sTNF-R1 and of sTNF-R2 were dramatically increased (p < 0.01), with little or no variation during treatment. While the IL-1b 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).
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