Brevetoxin inhalation alters the pulmonary response to influenza A in the male F344 rat.
Epidemiological studies demonstrated that the number of emergency-room visits for respiratory indications increases during periods of Florida Red Tides. The purpose of this study was to examine whether or not repeated brevetoxin inhalation, as may occur during a Florida Red Tide, affects pulmonary responses to influenza A. Male F344 rats were divided into four groups: (1) sham aerosol/no influenza; (2) sham aerosol/influenza; (3) brevetoxin/no influenza; and (4) brevetoxin/influenza. Animals were exposed by nose-only inhalation to vehicle or 50 μg brevetoxin-3/m3, 2 h/d for 12 d. On d 6 of aerosol exposure, groups 2 and 4 were administered 10,000 plaque-forming units of influenza A, strain HKX-31 (H3N2), by intratracheal instillation. Subgroups were euthanized at 2, 4, and 7 d post influenza treatment. Lungs were evaluated for viral load, cytokine content, and histopathologic changes. Influenza virus was cleared from the lungs over the 7-d period; however, there was significantly more virus remaining in the group 4 lungs compared to group 2. Influenza virus significantly increased interleukins-1α and -6 and monocyte chemotactic protein-1 in lung; brevetoxin exposure significantly enhanced the influenza-induced response. At 7 d, the severity of perivascular and peribronchiolar inflammatory cell infiltrates was greatest in group 4. Bronchiolitis persisted, with low incidence and severity, only in group 4 at d 7. These results suggest that repeated inhalation exposure to brevetoxin may delay virus particle clearance and recovery from influenza A infection in the rat lung.
Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA. jbenson@lrri.org
Janet M
JM
Benson
Molly L
ML
Wolf
Adriana
A
Kajon
Brad M
BM
Tibbetts
Andrea J
AJ
Bourdelais
Daniel G
DG
Baden
Thomas H
TH
March
D000281:Administration, Intranasal; D000818:Animals; D001990:Bronchiolitis, Viral / Q000276:immunology / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004198:Disease Susceptibility; D057097:Harmful Algal Bloom; D018928:Immunity, Mucosal / Q000187:drug effects; D053122:Influenza A Virus, H3N2 Subtype / Q000254:growth & development* / Q000276:immunology / Q000302:isolation & purification; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008297:Male; D008387:Marine Toxins / Q000008:administration & dosage / Q000633:toxicity*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D035964:Oxocins / Q000008:administration & dosage / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D019562:Viral Load; D000095702:Polyether Toxins
D016207:Cytokines; D008387:Marine Toxins; D035964:Oxocins; C546612:brevetoxin 3; D000095702:Polyether Toxins
Environ Health Perspect. 2005 May;113(5):644-9
15866778
Fundam Appl Toxicol. 1994 Jul;23(1):125-31
7958556
Environ Health Perspect. 2009 Aug;117(8):1239-43
19672403
Environ Health Perspect. 2005 May;113(5):626-31
15866775
Harmful Algae. 2010 Feb 1;9(2):186-189
20161504
Harmful Algae. 2006 Oct 1;5(5):526-533
20357898
Harmful Algae 2002 (2002). 2004;10:502-504
26436144
J Toxicol Environ Health A. 2004 Sep 24;67(18):1443-56
15371231
Immunopharmacol Immunotoxicol. 1989;11(2-3):421-43
2621324
Arch Toxicol. 2005 Nov;79(11):683-8
15986201
Chest. 2007 Jan;131(1):187-94
17218574
Environ Health Perspect. 2005 May;113(5):650-7
15866779
Environ Health Perspect. 2002 Feb;110(2):179-85
11836147
Toxicon. 1981;19(4):455-62
7199210
Curr Protoc Microbiol. 2009 May;Chapter 15:Unit 15G.3
19412911
Environ Health Perspect. 2009 Jul;117(7):1095-100
19654919
Environ Health Perspect. 2005 May;113(5):618-20
15866773
J Immunol. 2007 Dec 1;179(11):7220-4
18025163
Toxicology. 1994 Jul 1;91(2):179-88
8059441
Am J Public Health. 1997 Dec;87(12):1944-50
9431281
Curr Top Microbiol Immunol. 1986;128:1-54
3533447
J Toxicol Environ Health. 1991 Oct;34(2):259-73
1920529
J Gen Virol. 2005 Oct;86(Pt 10):2823-2830
16186238
Arch Toxicol. 2009 Nov;83(11):1009-19
19536525