Increased interleukin-6 production during the acute phase of the syndrome of episodic angioedema and hypereosinophilia.

Abstract

The Gleich syndrome is rare and associates recurrent angioedema, urticaria, fever, weight gain and blood hypereosinophilia, underlying systemic and local inflammation. The pathogenesis of those symptoms remains unclear. We wanted to address the possible implication of Interleukin-6 (IL-6) in the development of those clinical features, and to identify the cells involved in its production. A 26-year-old man suffering of this disease was referred in hospital. During an acute attack with weight gain, fever and a diffuse oedema, a marked increase in eosinophils count (42700/mm3 was observed. Serum ECP was elevated at 47 microg/L (normal less than 16). Corticosteroid therapy administrated on the 7th day was followed by a rapid remission. Blood samples were collected (before, during the attack and under corticosteroid therapy) for measurements of serum IL-6 (ELISA, Immunotech, Marseille, France) and plasma histamine (RIA, Immunotech, Marseille, France). Blood monocytes and eosinophils were isolated and a skin biopsy was performed during the attack. The plasma histamine level was within normal range. The level of IL-6 in sera peaked to 74 pg/mL, concomitant with the peak of eosinophilia at the acute phase phase of the attack. Under corticosteroids, we observed a drop in the IL-6 serum level to 29 pg/mL, concomitant with the clinical remission. During the attack, an increase in IL-6 production was observed in 24 h blood monocyte supernatants (11.10(3) pg/mL compared with 2.4+/-0.8.10(3) pg/mL for BM from controls) as well as in skin endothelial cells but not in the blood and skin eosinophils. In vitro, when endothelial cells were incubated in eosinophils supernatants of the patient, liberation of IL-6 was observed (3.3 10(3) pg/mL compared with controls: 2.1 10(3) pg/mL) CONCLUSION: Serum IL-6 elevation may be related to an increased production by blood monocytes and endothelial cells, possibly stimulated by eosinophil mediator during the acute phase of the disease, and might participate in the inflammatory reaction of this syndrome.