INFLUENCE OF INTERLEUKIN-8 CHALLENGE IN THE NASAL-MUCOSA IN ATOPIC AND NONATOPIC SUBJECTS

Interleukin-8 (IL-8) is a major cytokine in the recruitment of neutrop hils (polymorphonuclear leukocytes) to areas of inflammation. It also activates T lymphocytes and cytokine-primed basophils and eosinophils and therefore may be implicated as an effector in allergic inflammatio n. IL-8 has also been identified as a mediator in such inflammatory pu lmonary conditions as cystic fibrosis, allergen challenge, and sarcoid osis. To investigate the bioactivity of IL-8 in humans, we examined th e effects of nasal challenge with human recombinant IL-8 in a double-b lind placebo-controlled crossover study in which nasal resistance and rhinitic symptoms were monitored for 4 h after challenge. Cellular inf iltration was quantified on differentially stained nasal smears obtain ed at hourly intervals. Cellular responses caused by in vivo priming w ere assessed by a comparison of atopic and nonatopic patient groups. A significant neutrophilic infiltrate in smear samples was observed in all patients challenged with IL-8 from 12 +/- 4% (mean +/- SEM) at bas eline to 60 +/- 6% after 4 h; placebo challenge resulted in an increas e in neutrophils to 30 +/- 4% (p < 0.04). Additionally, a significant increase in cumulative eosinophil recruitment occurred over the challe nge period. Nasal resistance was significantly increased 10 min after instillation of IL-8 in all subjects compared with placebo, but there was no difference between atopic and nonatopic subjects. Nasal rhiniti c symptoms were also increased in all subjects receiving IL-8 compared with placebo. In a further study in 19 subjects, nasal biopsy was per formed 3 h after IL-8 or placebo challenge. Significantly increased ne utrophil infiltration was observed following 11-8 challenge compared w ith placebo challenge (32.4 +/- 10.0 and 7.2 +/- 2.0 cells/mm(2), resp ectively; p < 0.037, t test). We conclude that IL-8 may be an importan t cytokine that contributes to rhinitic symptomatology and to both neu trophil and eosinophil influx in the respiratory mucosa.