Effects of inhaled brevetoxins in allergic airways: toxin-allergen interactions and pharmacologic intervention.

Publisher: National Institute of Environmental Health Sciences Country of Publication: United States NLM ID: 0330411 Publication Model: Print Cited Medium: Print ISSN: 0091-6765 (Print) Linking ISSN: 00916765 NLM ISO Abbreviation: Environ Health Perspect Subsets: MEDLINE

Original Publication: Research Triangle Park, N. C. National Institute of Environmental Health Sciences.

Inhalation Exposure*; Allergens/*adverse effects ; Bronchoconstriction/*drug effects ; Dinoflagellida/*pathogenicity ; Marine Toxins/*toxicity ; Oxocins/*toxicity; Airway Resistance/drug effects ; Allergens/immunology ; Animals ; Asthma/etiology ; Asthma/physiopathology ; Eutrophication ; Female ; Sheep

During a Florida red tide, brevetoxins produced by the dinoflagellate Karenia brevis become aerosolized and cause airway symptoms in humans, especially in those with pre-existing airway disease (e.g., asthma). To understand these toxin-induced airway effects, we used sheep with airway hypersensitivity to Ascaris suum antigen as a surrogate for asthmatic patients and studied changes in pulmonary airflow resistance (R(L) after inhalation challenge with lysed cultures of K. brevis (crude brevetoxins). Studies were done without and with clinically available drugs to determine which might prevent/reverse these effects. Crude brevetoxins (20 breaths at 100 pg/mL; n = 5) increased R(L) 128 +/- 6% (mean +/- SE) over baseline. This bronchoconstriction was significantly reduced (% inhibition) after pretreatment with the glucocorticosteroid budesonide (49%), the beta(2) adrenergic agent albuterol (71%), the anticholinergic agent atropine (58%), and the histamine H1-antagonist diphenhydramine (47%). The protection afforded by atropine and diphenhydramine suggests that both cholinergic (vagal) and H1-mediated pathways contribute to the bronchoconstriction. The response to cutaneous toxin injection was also histamine mediated. Thus, the airway and skin data support the hypothesis that toxin activates mast cells in vivo. Albuterol given immediately after toxin challenge rapidly reversed the bronchoconstriction. Toxin inhalation increased airway kinins, and the response to inhaled toxin was enhanced after allergen challenge. Both factors could contribute to the increased sensitivity of asthmatic patients to toxin exposure. We conclude that K. brevis aerosols are potent airway constrictors. Clinically available drugs may be used to prevent or provide therapeutic relief for affected individuals.

J Allergy Clin Immunol. 1988 Jun;81(6):1187-91. (PMID: 3379231)
Am J Respir Crit Care Med. 1994 Mar;149(3 Pt 1):687-93. (PMID: 8118638)
FASEB J. 1989 May;3(7):1807-17. (PMID: 2565840)
Environ Health Perspect. 2005 May;113(5):650-7. (PMID: 15866779)
Am Rev Respir Dis. 1987 Jan;135(1):176-80. (PMID: 3541715)
J Clin Invest. 1994 Feb;93(2):776-87. (PMID: 8113411)
J AOAC Int. 1995 Mar-Apr;78(2):499-508. (PMID: 7538840)
Harmful Algae. 2004 Apr 1;3(2):99-115. (PMID: 20411030)
J Appl Physiol (1985). 2002 Dec;93(6):1900-6. (PMID: 12433933)
Environ Toxicol Chem. 2001 Jan;20(1):107-14. (PMID: 11351396)
Bull Environ Contam Toxicol. 2003 Jan;70(1):161-5. (PMID: 12478439)
Toxicon. 1988;26(10):961-3. (PMID: 3201483)
Am J Physiol Lung Cell Mol Physiol. 2004 Apr;286(4):L734-40. (PMID: 14660481)
J Appl Physiol Respir Environ Exerc Physiol. 1984 Oct;57(4):1182-8. (PMID: 6209256)
J Appl Physiol (1985). 1997 Sep;83(3):784-91. (PMID: 9292464)
Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):603-11. (PMID: 10934094)
Bull Environ Contam Toxicol. 1992 Oct;49(4):479-84. (PMID: 1421838)
J Appl Physiol (1985). 1992 Sep;73(3):1093-101. (PMID: 1383185)
J Appl Physiol (1985). 1995 Dec;79(6):1966-70. (PMID: 8847261)
Environ Health Perspect. 2005 May;113(5):644-9. (PMID: 15866778)
Am J Respir Cell Mol Biol. 1999 Dec;21(6):666-74. (PMID: 10572063)
Am J Respir Crit Care Med. 2004 Jan 1;169(1):97-104. (PMID: 14578216)
Am J Respir Crit Care Med. 2005 Jan 1;171(1):26-34. (PMID: 15447946)
J Allergy Clin Immunol. 1982 May;69(5):418-28. (PMID: 7200498)
J Appl Physiol (1985). 1992 May;72(5):1831-7. (PMID: 1318295)
J Appl Physiol (1985). 1993 Apr;74(4):1492-8. (PMID: 7685753)
Am J Respir Crit Care Med. 1996 Sep;154(3 Pt 1):649-53. (PMID: 8810600)
J Allergy Clin Immunol. 1991 Feb;87(2):557-64. (PMID: 1704388)
J Appl Physiol Respir Environ Exerc Physiol. 1981 Dec;51(6):1651-6. (PMID: 7319895)
Am J Respir Crit Care Med. 1996 Jul;154(1):36-42. (PMID: 8680696)
J Appl Physiol Respir Environ Exerc Physiol. 1980 May;48(5):789-93. (PMID: 7451287)
J Appl Physiol (1985). 2000 Oct;89(4):1397-402. (PMID: 11007574)

P01 ES010594 United States ES NIEHS NIH HHS; P01 ES010594-05 United States ES NIEHS NIH HHS; P01 ES 10594 United States ES NIEHS NIH HHS

0 (Allergens)
0 (Marine Toxins)
0 (Oxocins)
98225-48-0 (brevetoxin)

Date Created: 20050504 Date Completed: 20050816 Latest Revision: 20181113

20221213

PMC1257560

10.1289/ehp.7498

15866776