EXPRESSION AND RELEASE OF INTERLEUKIN-8 BY HUMAN AIRWAY SMOOTH-MUSCLECELLS - INHIBITION BY TH-2 CYTOKINES AND CORTICOSTEROIDS

Interleukin (IL)-8 is a C-X-C chemokine that potently chemoattracts an d activates neutrophils. We determined whether IL-8 could be produced by human airway smooth muscle cells in culture and examined its regula tion, TNF-alpha stimulated IL-8 mRNA expression and protein release in a time- and dose-dependent manner, whereas IFN-gamma alone had no eff ect, Both cytokines together did not induce greater IL-8 release compa red to TNF-alpha alone, IL-1 beta was more potent in inducing IL-8 rel ease and. together with TNF-alpha, there was a synergistic augmentatio n of IL-8 release. IL-8 release induced by TNF-alpha and IFN-gamma was partly inhibited by the Th-2-derived cytokines IL-4, IL-10, and IL-13 , as well as by dexamethasone. In addition to its contractile response s, airway smooth muscle cells have synthetic and secretory potential w ith the release of IL-8 and subsequent recruitment and activation of n eutrophils in the airways. Release of IL-8 can be modulated by Th-2-de rived cytokines and corticosteroids.