- Paper Report
- Open Access
Exercise asthma and inflammatory cytokines
- Jeffrey Fedan1
© Biomed Central Ltd 2001
- Received: 27 October 2000
- Accepted: 19 September 2001
- Published: 19 September 2001
- Exercise asthma, hyperosmolarity, inhaled steroids, MAP kinase pathways
Exercise elicits airway obstruction in asthmatic patients (exercise-induced asthma, [EA]), which may be manifest as early and late phases, the latter involving an inflammatory component. The mechanisms involved in EA have not been clarified, but released mediators (eg histamine) may play a role. During exercise the airway wall cools by a few degrees and the airway surface liquid (ASL) becomes somewhat hyperosmotic (40-60 mOsm) due to evaporative water loss. The authors have investigated whether hyperosmotic solution or cooling and re-warming of cultured bronchial epithelial cells (BEC) gives rise to the release of pro-inflammatory mediators (interleukin [IL]-8 and RANTES [regulated upon activation, normal T cell expressed and secreted]) and activation of mitogen-activated protein (MAP) kinase pathways (p38 and c-Jun-NH2-terminal kinase [JNK]) and whether two inhaled steroids used to treat asthma inhibit these responses.
A 10 min challenge of the BEC with 1280 mOsm/kg solution (increased by approximately 990 mOsm/kg over culture medium by adding NaCl) elicited within 24 hr the production of IL-8 and RANTES. This response was inhibited by budesonide or beclomethasone following pretreatment (1 h) with the steroid. Likewise, cooling (to 0RC for 2 h) and rewarming (to 37°#C) stimulated IL-8 and RANTES production in a seroid-inhibitable manner. Responses to hyperosmolarity were approximately 10-fold greater than responses to temperature jumps. Cooling of the cells, and hyperosmolar challenge, led to activation of p38 and JNK, but these responses were not blocked by the steroids. The release of inflammatory mediators could contribute to the late phase inflammatory response in EA.
Cell culture, western blots
- Hashimoto S, Gon Y, Matsumoto K, Takeshita I, Maruoka S, Horie T: Inhalant corticosteroids inhibit hyperosmolarity-induced, and cooling and rewarming-induced interleukin-8 and RANTES production by human bronchial epithelial cells. Am J Respir Crit Care Med. 2000, 162: 1075-1080.View ArticleGoogle Scholar