Antieosinophil action of IL-12 in human polyp culture

Abstract

RATIONALE: Tissue eosinophilia is an important pathophysiological issue in bronchial asthma and nasal polyps. Its magnitude is regulated by several mechanisms, including selective migration of eosinophils to peripheral tissues and prolongation of survival. A key role in this processes is assigned to Th2 originating cytokines: IL-3, IL-5, GM-CSF. It has been previously demonstrated that IL-12 diminishes tissue eosinophilia in an animal model, and Hofstra showed that IL-12 together with IL-18 prevents allergen-induced increase bronchial hyperresponsiveness, BAL eosinophilia and the development of allergen-specific Th2 cells. METHODS: Nasal polyps were obtained during routine surgery and were cultured in fragments of approximately 30 mg for 2, 6, and 15 days in RPMI 1640 in the absence or presence of IL-12. Afterwards a dose-dependency was tested at day 2 of culture. Polyp tissue from cultures was than processed to slides, stained with Giemsa and cells were counted in light microscopy (400x). RESULTS: Eosinophils represented 62.8+/-21.3% of residing cells in nasal polyps at the day 0. IL-12 (1 microg/ml) caused a significant time-dependent decrease in the percentage of Eos after 2 and 6 days. The effect of IL-12 at day 2 was concentration-dependent: control, 28.2+/-2.9; at 10 ng/ml, 13.9+/-6.4 (n=4, p<0.05); at 100 ng/ml, 11.6+/-2.1 (p<0.01); at 1 microg/ml, 7.5+/-1.5 (p<0.005). CONCLUSION: IL-12 acts as potent topical antieosinophilic agent. Its action can be seen in a cultured polyp environment. It is visible already after two days and is concentration-dependent. Further study is needed to elucidate tissue mechanisms of this action.