SYNTHESIS OF INTERLEUKIN-1-ALPHA, INTERLEUKIN-6, AND INTERLEUKIN-8 BYCULTURED HUMAN NASAL EPITHELIAL-CELLS

Nasal epithelium forms the initial barrier between the environment and the respiratory system and may be a potential source of proinflammato ry interleukins, which contribute to the pathophysiology of allergic a nd nonallergic rhinitis. To explore this possibility, epithelium and c ultured human nasal epithelial cells from nasal turbinates of patients undergoing surgery for treatment of upper airway obstruction were exa mined for the spontaneous expression of interleukin (TL)-1 alpha, IL-1 beta, IL-6, and IL-8. Human nasal epithelial cell lysates and culture supernatants were assayed by two-site ELISAs specific for IL-1 alpha, IL-1 beta, IL-6, or IL-8. Maximum concentrations of these cytokines i n supernatants ranged from approximately 0.2 to 2 ng/ml for IL-1 alpha , 1.5 to 7 ng/ml for IL-6 and 100 to 3000 ng/ml for IL-8. IL-1 alpha w as predominantly cell-associated, whereas most of the IL-8 and all of the IL-6 were detected in the supernatant. Little or no IL-1 beta was detected by ELISA in the supernatants or cell lysates. Whole tissue tu rbinates and isolated epithelium were also examined for IL-1 beta, IL- 6, and IL-8 mRNA expression by Northern blot analysis. IL-6 and IL-8 m RNAs were detected, whereas IL-1 beta mRNA was not. Furthermore, IL-6 and IL-8 release from human nasal epithelial cell cultures was enhance d by addition to the cultures of lipopolysaccharide, and IL-6 release was inhibited by polymyxin B. Thus human nasal epithelium may be a maj or source of IL-1 alpha, IL-6, and IL-8 in allergic and nonallergic rh initis. Production of those proinflammatory cytokines by epithelial ce lls of the nasal and sinus mucosa may contribute to the pathologic and clinical events that occur in these diseases.