IMMUNOGLOBULIN-D ENHANCES THE RELEASE OF TUMOR-NECROSIS-FACTOR-ALPHA,AND INTERLEUKIN-1-BETA AS WELL AS INTERLEUKIN-1 RECEPTOR ANTAGONIST FROM HUMAN MONONUCLEAR-CELLS

Immunoglobulin D (IgD) is normally present in only low concentrations in serum. In the hyper-IgD and periodic fever syndrome (HIDS), however , serum levels exceed 140 mg/l. This syndrome is further characterized by recurrent inflammatory febrile attacks together with an acute phas e response and appearance of cytokines in the circulation. The role of IgD in the pathogenesis of HIDS and its relation to the increased cyt okine concentrations is unclear. Therefore, we tested whether IgD, Ige and alpha(1)-acid glycoprotein (AGP) isolated from human serum influe nce the synthesis of interleukin-1 beta (IL-1 beta), tumour necrosis f actor-alpha (TNF-alpha), and IL-lra, as measured by specific radioimmu noassays, in human peripheral blood mononuclear cells (PBMC). Incubati on of PBMC with IgD and AGP for 24 hr led to increased release of IL-1 beta, TNF-alpha, and IL-1ra. The magnitude of stimulation of IgD exce eded that of AGP; the effect by IgD was dose-dependent and showed a 30 -fold (TNF-alpha) to almost 150-fold (IL-1 beta) increase at the highe st concentration (50 mg/l), while AGP (750 mu g/ml) only increased the cytokine secretion fourfold (TNF-alpha) to almost 30-fold (IL-1 beta) . The effect of IgD on IL-1ra was less dramatic but a fivefold increas e was observed at 50 mg/l compared with a 2.5-fold increase with AGP. IgD potentiated the effect of lipopolysaccharide (LPS) on secretion of both IL-1 beta and TNF-alpha, although the effect was most apparent f or TNF-alpha. Apart from inducing IL-lra synthesis, IgG did not influe nce cytokine release in human PBMC. These data indicate that IgD is a potent inducer of TNF-alpha, IL-1 beta and IL-1ra and thus may contrib ute to the pathogenesis of HIDS.