Mucosal IL-12 inhibits airway reactivity to methacholine and respiratory failure in murine asthma

Sanjiv Sur, P. Bouchard, D. Holbert, M. R. Van Scott

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The worldwide incidence, prevalence, and fatality rates from asthma are increasing despite currently available therapeutic modalities. Systemic administration of interleukin (IL)-12 has been shown to inhibit airway reactivity in murine models of asthma, but the required dosage is high and may be toxic. This study tested the hypothesis that IL-12 administered directly into the lungs is more effective in inhibiting airway reactivity than systemically administered IL-12, allowing lower doses to be used. A low dose (10 ng) of IL-12 was delivered either intratracheally (mucosal delivery) or intraperitoneally (systemic delivery) at the time of ragweed (RW) challenge in mice sensitized to RW. Basal airway resistance and airway reactivity to methacholine were measured 3 days after RW challenge. Compared to phosphate-buffered saline (PBS) challenge of RW sensitized mice, RW challenge increased basal resistance and the slope of the methacholine dose-response curve. Methacholine challenge of RW-challenged mice also induced premature respiratory failure (respiratory rate < 150/min, tidal volume < 0.15 mL) in some animals. Administration of mucosal or systemic IL-12 at the time of RW challenge decreased basal airway resistance. However, only mucosal IL-12 decreased airway reactivity and inhibited respiratory failure during methacholine challenge. These findings indicate that mucosal delivery of a low dose of IL-12 is more effective than systemic IL-12 in inhibiting airway reactivity and respiratory failure in a mouse model of asthma.

Original languageEnglish (US)
Pages (from-to)477-489
Number of pages13
JournalExperimental Lung Research
Volume26
Issue number6
StatePublished - 2000

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Keywords

  • Airway reactivity
  • Asthma
  • Respiratory failure

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Sur, S., Bouchard, P., Holbert, D., & Van Scott, M. R. (2000). Mucosal IL-12 inhibits airway reactivity to methacholine and respiratory failure in murine asthma. Experimental Lung Research, 26(6), 477-489.