Pemphigus vulgaris: The role of IL-1 and IL-1 receptor antagonist in pathogenesis and effects of intravenous immunoglobulin on their production

Intravenous immunoglobulin (IVIG) is increasingly being used for the treatm ent of autoimmune diseases. In the present report, the role of IVIG on in v ivo and in vitro production of IL-1 and IL-1 receptor antagonist (Ra) was s tudied in patients with pemphigus vulgaris (PV). Serum samples from 20 untr eated patients with active PV prior to initiation of systemic therapy, 20 p atients receiving IVIG treatment, 20 patients in clinical remission after c onventional therapy, and 20 normal human controls were studied to determine the serum levels of IL-1 alpha, IL-1 beta, and IL-1Ra. The in vitro produc tion of these cytokines was measured in the culture supernatant of peripher al blood mononuclear cells (PBMC) from 10 PV patients immediately before an d after IVIG therapy and from age and sex-matched 10 healthy donors simulta neously. Elevated levels of IL-1 alpha and IL-1 beta were detected (i) in t he serum of untreated PV patients with active disease prior to systemic the rapy and (ii) before IVIG infusions in patients receiving IVIG therapy. The se increased levels are statistically significant when compared to the leve ls in healthy controls (P < 0.01). A marked reduction of IL-1 alpha and IL- 1 beta was detected (i) in the serum of patients in prolonged clinical remi ssion and (ii) immediately after IVIG infusion in those patients on MG ther apy. Increased level of IL-1Ra was detected in PV patients in prolonged cli nical remission and after IVIG infusion in those receiving IVIG therapy. Th ese differences were statistically significant when compared to the levels in normal controls and to the levels in the sera of patients with active di sease (P < 0.01) or just before the beginning of IVIG infusion (P < 0.01). Similar differences in the levels of IL-1 alpha, IL-1 beta, and IL-1Ra were found in the culture supernatant of PBMC isolated from the PV patients pre and post IVIG therapy. These observations suggests that, compared to norma l controls, patients with active PV have reversed levels of IL-1 alpha, IL- 1 beta, and IL-1Ra. IVIG therapy may down-regulate production of IL-1 alpha and IL-1 beta and enhance production of IL-1Ra, in vivo and in vitro. This might be one of the important mechanisms by which IVIG produces its early therapeutic effects in pemphigus vulgaris. (C) 2001 Academic Press.