The effect of the oral leukotriene antagonist, ICI 204,219, on leukotriene D4 and histamine-induced cutaneous vascular reactions in man

Jonathan A. Bernstein; Paul A. Greenberger; Roy Patterson; Mitchell Glass; Robert Krell; Per T. Thyrums

doi:10.1016/0091-6749(91)90217-C

The effect of the oral leukotriene antagonist, ICI 204,219, on leukotriene D₄ and histamine-induced cutaneous vascular reactions in man

Jonathan A. Bernstein, Paul A. Greenberger^*, Roy Patterson, Mitchell Glass, Robert Krell, Per T. Thyrums

^*Corresponding author for this work

Medicine, Allergy Division

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

Eighteen normal male subjects were recruited for a double-blind, placebo-controlled, randomized, two-period crossover study to determine the effects of a new, potent, highly selective, oral peptide leukotriene antagonist (ICI 204,219) on cutaneous vasculture. Skin testing for leukotriene D₄ (LTD₄) and histamine was performed at three different time intervals after receiving ICI 204,219 or placebo. The LTD₄ threshold dose responses were recorded in duplicate to verify reproducibility. These data confirm known remarkable dose-response variation of cutaneous vascular reactions to LTD₄ since some subjects reacted to a dose as low as 0.001 fmol. Twelve subjects (67%) demonstrated a more than one-half log increase in their threshold response after receiving ICI 204,219. Five of these 12 subjects (28%) had >1 log-dose response after ICI 204,219. Two of these subjects (11.1%) had a 5 or 10 log increase in their threshold response after receiving ICI 204,219. Given the role of leukotrienes as potentially important mediators in immediate-type reactions, our results raise the possibility for additional investigation of the antagonistic effect of ICI 204,219 in nonallergic and allergic cutaneous diseases.

Original language	English (US)
Pages (from-to)	93-98
Number of pages	6
Journal	The Journal of allergy and clinical immunology
Volume	87
Issue number	1 PART 1
DOIs	https://doi.org/10.1016/0091-6749(91)90217-C
State	Published - Jan 1991

Funding

From the Sections of Allergy-Immunology, Department of Medi-tine, Northwestern University Medical School, Chicago, Ill., and *ICI Pharmaceuticals Group, Wilmington, Del. Supported by United States Public Health Services Grant AI 11403 and the Ernest S. Bazlev Grant. Received for publication Jan. 23, 1990. Revised Aug. 6, 1990. Accepted for publication Aug. 14, 1990. Reprint requests: Paul A. Greenberger, MD, Northwestern Uni-versity Medical School, 303 E. Chicago, Ave., Chicago, IL 60611. l/1/24691

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1016/0091-6749(91)90217-C

Cite this

@article{4675bdce4ca545d9a199b30839edaa8b,

title = "The effect of the oral leukotriene antagonist, ICI 204,219, on leukotriene D4 and histamine-induced cutaneous vascular reactions in man",

abstract = "Eighteen normal male subjects were recruited for a double-blind, placebo-controlled, randomized, two-period crossover study to determine the effects of a new, potent, highly selective, oral peptide leukotriene antagonist (ICI 204,219) on cutaneous vasculture. Skin testing for leukotriene D4 (LTD4) and histamine was performed at three different time intervals after receiving ICI 204,219 or placebo. The LTD4 threshold dose responses were recorded in duplicate to verify reproducibility. These data confirm known remarkable dose-response variation of cutaneous vascular reactions to LTD4 since some subjects reacted to a dose as low as 0.001 fmol. Twelve subjects (67%) demonstrated a more than one-half log increase in their threshold response after receiving ICI 204,219. Five of these 12 subjects (28%) had >1 log-dose response after ICI 204,219. Two of these subjects (11.1%) had a 5 or 10 log increase in their threshold response after receiving ICI 204,219. Given the role of leukotrienes as potentially important mediators in immediate-type reactions, our results raise the possibility for additional investigation of the antagonistic effect of ICI 204,219 in nonallergic and allergic cutaneous diseases.",

author = "Bernstein, {Jonathan A.} and Greenberger, {Paul A.} and Roy Patterson and Mitchell Glass and Robert Krell and Thyrums, {Per T.}",

note = "Funding Information: From the Sections of Allergy-Immunology, Department of Medi-tine, Northwestern University Medical School, Chicago, Ill., and *ICI Pharmaceuticals Group, Wilmington, Del. Supported by United States Public Health Services Grant AI 11403 and the Ernest S. Bazlev Grant. Received for publication Jan. 23, 1990. Revised Aug. 6, 1990. Accepted for publication Aug. 14, 1990. Reprint requests: Paul A. Greenberger, MD, Northwestern Uni-versity Medical School, 303 E. Chicago, Ave., Chicago, IL 60611. l/1/24691",

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AU - Glass, Mitchell

AU - Krell, Robert

AU - Thyrums, Per T.

N1 - Funding Information: From the Sections of Allergy-Immunology, Department of Medi-tine, Northwestern University Medical School, Chicago, Ill., and *ICI Pharmaceuticals Group, Wilmington, Del. Supported by United States Public Health Services Grant AI 11403 and the Ernest S. Bazlev Grant. Received for publication Jan. 23, 1990. Revised Aug. 6, 1990. Accepted for publication Aug. 14, 1990. Reprint requests: Paul A. Greenberger, MD, Northwestern Uni-versity Medical School, 303 E. Chicago, Ave., Chicago, IL 60611. l/1/24691

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N2 - Eighteen normal male subjects were recruited for a double-blind, placebo-controlled, randomized, two-period crossover study to determine the effects of a new, potent, highly selective, oral peptide leukotriene antagonist (ICI 204,219) on cutaneous vasculture. Skin testing for leukotriene D4 (LTD4) and histamine was performed at three different time intervals after receiving ICI 204,219 or placebo. The LTD4 threshold dose responses were recorded in duplicate to verify reproducibility. These data confirm known remarkable dose-response variation of cutaneous vascular reactions to LTD4 since some subjects reacted to a dose as low as 0.001 fmol. Twelve subjects (67%) demonstrated a more than one-half log increase in their threshold response after receiving ICI 204,219. Five of these 12 subjects (28%) had >1 log-dose response after ICI 204,219. Two of these subjects (11.1%) had a 5 or 10 log increase in their threshold response after receiving ICI 204,219. Given the role of leukotrienes as potentially important mediators in immediate-type reactions, our results raise the possibility for additional investigation of the antagonistic effect of ICI 204,219 in nonallergic and allergic cutaneous diseases.

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