We hypothesized that the peculiar mixed interleukin-4 (IL-4/Th2) and interferon gamma INF-γ (INF-γ/Th1) inflammatory milieu found in the airways of patients with aspirin-exacerbated respiratory disease (AERD) is responsible for the altered regulation of the IL-1β/IL-1RI-/EP₂/COX-2 autocrine loop also found in these patients. The objective of the study is to demonstrate that IL-4 and INF-γ cytokines, are capable of inducing in healthy nasal mucosa (NM) the dysregulation of the autocrine loop of COX reported in AERD.

Fibroblasts were obtained from NM (n = 8). To evaluate the role of IL-4 and IFN-γ on the autocrine loop, fibroblasts were incubated with or without IL-1β, in the presence or absence of IL-4 and/or IFN-γ for 48 h. After this period, the expression of EP₂, EP₃, EP₄, IL-1RI, COX-2 and mPGES-1 was measured by Western blot.

Stimulation of fibroblasts with IL-1β significantly increased the expression of EP₂, but had no effects on EP₃ and EP₄ expression Incubation with IL-4 or IFN-γ alone was not able to modify the expression of any of the components of the autocrine loop. In contrast, co-treatment with IL-4 and IFN-γ was able to significantly inhibit IL-1β-induced EP₂, IL-1RI, COX-2 and mPGES-1.

These results suggest that the mixed Th1/Th2 inflammatory pattern found in the airways of AERD patients might be responsible for the altered regulation of the COX pathway also reported in these asthma patients.