Secretory leukocyte protease inhibitor prevents allergen-induced pulmonary responses in animal models of asthma

Clifford D. Wright, Andrew M. Havill, Scot C. Middleton, Mohammed A. Kashem, Patrice A. Lee, David J. Dripps, Thomas G. O'Riordan, Michael P. Bevilacqua, William M. Abraham

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways that exhibits broad spectrum inhibitory activity against mast cell and leukocyte serine proteases implicated in asthma pathology. To assess the potential therapeutic utility of SLPI in this disorder, its effects on antigen-induced pulmonary responses were evaluated. In Ascaris-sensitized sheep, SLPI (3 mg) administered by aerosol daily for 4 days, with the final dose 0.5 h before antigen challenge, reduced the areas under the curve for early- and late-phase bronchoconstriction (73 and 95%, respectively; p < .05 versus control responses). SLPI also inhibited the development of airway hyperresponsiveness to carbachol (84%, p < .05 versus control response) measured 24 h after antigen challenge. In ovalbumin- sensitized guinea pigs, intratracheal administration of SLPI daily for 3 days, with the final dose 1 h before antigen challenge, inhibited the development of airway hyperresponsiveness to histamine with an ED50 of <0.05 mg/kg. Prolonged pharmacodynamic activity of SLPI was observed in both species. in a murine model of atopic asthma, SLPI inhibited leukocyte influx into the airways after chronic allergen challenge. SLPI administered to sheep by the predosing protocol described above also prevented the antigen-induced decrease of tracheal mucus velocity (p < .05). In addition, a single aerosol administration of SLPI (30 mg) to sheep 1 h after antigen challenge inhibited the subsequent late-phase bronchoconstriction and development of hyperresponsiveness and reversed the stimulated decrease in tracheal mucus velocity. These results suggest that SLPI may provide therapeutic intervention against the pathophysiology of asthma and its underlying pathology.

Original languageEnglish
Pages (from-to)1007-1014
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume289
Issue number2
StatePublished - May 1 1999
Externally publishedYes

Fingerprint

Secretory Leukocyte Peptidase Inhibitor
Allergens
Asthma
Animal Models
Lung
Antigens
Sheep
Bronchoconstriction
Mucus
Aerosols
Leukocytes
Pathology
Ascaris
Ovalbumin
Carbachol
Serine Proteases
Mast Cells
Histamine
Area Under Curve
Guinea Pigs

ASJC Scopus subject areas

  • Pharmacology

Cite this

Wright, C. D., Havill, A. M., Middleton, S. C., Kashem, M. A., Lee, P. A., Dripps, D. J., ... Abraham, W. M. (1999). Secretory leukocyte protease inhibitor prevents allergen-induced pulmonary responses in animal models of asthma. Journal of Pharmacology and Experimental Therapeutics, 289(2), 1007-1014.

Secretory leukocyte protease inhibitor prevents allergen-induced pulmonary responses in animal models of asthma. / Wright, Clifford D.; Havill, Andrew M.; Middleton, Scot C.; Kashem, Mohammed A.; Lee, Patrice A.; Dripps, David J.; O'Riordan, Thomas G.; Bevilacqua, Michael P.; Abraham, William M.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 289, No. 2, 01.05.1999, p. 1007-1014.

Research output: Contribution to journalArticle

Wright, CD, Havill, AM, Middleton, SC, Kashem, MA, Lee, PA, Dripps, DJ, O'Riordan, TG, Bevilacqua, MP & Abraham, WM 1999, 'Secretory leukocyte protease inhibitor prevents allergen-induced pulmonary responses in animal models of asthma', Journal of Pharmacology and Experimental Therapeutics, vol. 289, no. 2, pp. 1007-1014.
Wright, Clifford D. ; Havill, Andrew M. ; Middleton, Scot C. ; Kashem, Mohammed A. ; Lee, Patrice A. ; Dripps, David J. ; O'Riordan, Thomas G. ; Bevilacqua, Michael P. ; Abraham, William M. / Secretory leukocyte protease inhibitor prevents allergen-induced pulmonary responses in animal models of asthma. In: Journal of Pharmacology and Experimental Therapeutics. 1999 ; Vol. 289, No. 2. pp. 1007-1014.
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