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

Wegener's granulomatosis (WG) is a systemic inflammatory disease with vasculitis as the key feature. Abnormal expression of tumour necrosis factor alpha (TNF alpha) is considered of prime pathogenic importance in several inflammatory diseases. The effects of TNF alpha are mediated by TNF receptors (TNF-R), and these receptors are often found in soluble forms (sTNF-R), which can modulate TNF alpha actions. To evaluate the clinical importance of the TNF family of cytokines, the serum levels of TNF alpha, TNF beta, now termed lymphotoxin (LT alpha), 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 TNF alpha 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 TNF alpha levels. Examination of the relative amounts of TNF alpha and sTNF-R indicated that TNF alpha 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-1 beta 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).