Immunotherapy suppresses the production of monocyte chemotactic and activating factor and augments the production of IL-8 in children with asthma.

Abstract

Histamine-releasing factor consists of a group of cytokines that can cause basophils or mast cells to release histamine. However, the composition of histamine-releasing factor remains undefined. This study was done to measure the concentrations, in plasma and mononuclear cell culture supernatants from children with asthma, of chemokines that are known to contribute to histamine-releasing factor activity. Plasma and mononuclear cell culture supernatants were obtained from 25 children newly diagnosed with asthma, 25 good responders to immunotherapy, 23 poor responders, 25 patients with acute attacks, and 13 normal subjects. All the patient groups produced, spontaneously and after stimulation with phytohemagglutinin and mite allergen, greater amounts of monocyte chemotactic and activating factor, macrophage inflammatory protein-1 alpha, and RANTES (beta chemokines) and IL-8 and growth-related gene alpha (alpha chemokines) than did normal subjects. Successful immunotherapy resulted in decreased production, especially the spontaneous type, of beta chemokines that cause histamine release and in increased production of a chemokines that inhibit histamine release. Abnormal chemokine production may contribute to the pathogenesis of bronchial asthma, and restoration of normal chemokine production may be used to explain, in part, the clinical efficacy of immunotherapy.