CYTOKINE ACTIVATION DURING ATTACKS OF THE HYPERIMMUNOGLOBULINEMIA-D AND PERIODIC FEVER SYNDROME

The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, join t involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (>100 U/mL). This familial disorder has been diagnosed in 59 patients, mainly from Europe. The pathogenesis of this febrile disorder is unknown, but attacks are joined by an acute-phase response. Because this response is considered to be mediated by cytok ines, we measured the acute-phase proteins C-reactive protein (CRP) an d soluble type-II phospholipase A(2) (PLA(2)) together with circulatin g concentrations and ex vivo production of the proinflammatory cytokin es interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, and tumor necros is factor alpha (TNF alpha) and the inhibitory compounds IL-1 receptor antagonist (IL-1ra), IL-10. and the soluble TNF receptors p55 (sTNFr p55) and p75 (sTNFr p75) in 22 patients with the hyper-IgD syndrome du ring attacks and remission. Serum CRP and PLA, concentrations were ele vated during attacks (mean, 213 mg/L and 1,452 ng/mL, respectively) an d decreased between attacks. Plasma concentrations of IL-1 alpha, IL-1 beta, or IL-10 were not increased during attacks. TNF alpha concentra tions were slightly, but significantly, higher with attacks (104 v 117 pg/mL). Circulating IL-6 values increased with attacks (19.7 v 147.9 pg/mL) and correlated with CRP and PLA(2) values during the febrile at tacks. The values of the antiinflammatory compounds IL-1ra, sTNFr p55, and sTNFr p75 were significantly higher with attacks than between att acks, and there was a significant positive correlation between each. T he ex-vivo production of TNF alpha IL-1 beta, and IL-1ra was significa ntly higher with attacks, suggesting that the monocytes/macrophages we re already primed in vivo to produce increased amounts of these cytoki nes. These findings paint to an activation of the cytokine network, an d this suggests that these inflammatory mediators may contribute to th e symptoms of the hyper-IgD syndrome. (C) 1995 by The American Society of Hematology.