Modulation of IL-6 Release Subsequent to Airway Poly I:C Administration
Sunday, March 6, 2016
South Exhibit Hall H (Convention Center)
KarryAnne K. Belanger, B.Sc., Walter C. Spear, M.Sc., Barbara A. Rolls, Spotswood Miller, B.Sc., Bing Tian, PhD, Gracie Vargas, PhD, Massoud Motamedi, PhD, Istvan Boldogh, PhD, Allan Brasier, MD, Bill T. Ameredes, PhD
Rationale:  Interleukin(IL)-6 has been shown to be upregulated in animal models of airway injury with Polyinosinic:polycytidylic acid (Poly I:C), in early phases of inflammation (e.g., 24 hr). However, we investigated whether airway leukocytes would release significant amounts of IL-6, with quiescence of inflammation, 1 week after airway administration of Poly I:C, to determine whether cells remained primed for IL-6 release.

Methods:  C57Bl6 mice were administered intranasal Poly I:C (100, 500 mcg; n=5/group) daily, over 21 days. One week after the last challenge, bronchoalveolar lavage (BAL) fluid and leukocytes were collected, and cells were cultured (72 hr), with and without LPS (1000 ng/ml). IL-6 in both the BAL fluid and the culture media was measured by ELISA; data were compared by t-tests.

Results: BAL total cell counts (1.04 vs. 1.22 x105cells/ml) and IL-6 levels (all not detectable; <1.3 pg/ml) were not different between the low and high Poly I:C groups. Similarly, spontaneous IL-6 release from cultured leukocytes was not detectable with low Poly I:C, and averaged 24 pg/ml with high Poly I:C (n.s), suggesting quiescence of airway inflammation. With LPS stimulation, IL-6 release was significantly increased, both to levels greater than spontaneous (P<0.05), and in an LPS-concentration dependent fashion (1420 vs. 9068 pg/ml, P<0.05).

Conclusions:  We conclude that Poly I:C-induced airway injury results in leukocyte priming for stimulus-associated IL-6 release that is maintained beyond the early and late phases of airway inflammation, which may be important in cellular responses to subsequent triggers that can support cell proliferation, and possibly contribute to airway remodeling