Prior exposure to acrolein accelerates pulmonary inflammation in influenza A-infected mice.
The combustion product acrolein contributes to several smoke-related health disorders, but whether this immunomodulatory toxicant alters pulmonary susceptibility to viruses has received little attention. To study the effects of prior acrolein dosing on the severity of influenza A viral infection, male BALB/c mice received acrolein (1mg/kg) or saline (control) via oropharyngeal aspiration either 4- or 7-days prior to intranasal inoculation with either influenza A/PR/8/34 virus or vehicle. At 0, 2, 4 and 7 days post-inoculation, lung samples were assessed for histological changes while pulmonary inflammation was monitored by estimating immune cell numbers and cytokine levels in bronchoalveolar lavage fluid (BALF). After viral challenge, animals that were exposed to acrolein 4 days previously experienced greater weight loss and exhibited an accelerated inflammatory response at 2 days after viral inoculation. Thus compared to saline-pretreated, virus-challenged controls, BALF recovered from these mice contained higher numbers of macrophages and neutrophils in addition to increased levels of several inflammatory cytokines, including IL-1α, IL-1β, IL-6, TNF, IFN-γ, KC, and MCP-1. The acrolein-induced increase in viral susceptibility was suppressed by the carbonyl scavenger bisulphite. These findings suggest acute acrolein intoxication "primes" the lung to mount an accelerated immune response to inhaled viruses.
Pharmacology and Anaesthesiology Unit, School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia 6009, Australia.
Ferrer H C
FH
Ong
Peter J
PJ
Henry
Philip C
PC
Burcham
D000171:Acrolein / Q000633:toxicity*; D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000097:blood; D004198:Disease Susceptibility; D004334:Drug Administration Schedule; D016166:Free Radical Scavengers / Q000494:pharmacology; D009980:Influenza A virus / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology / Q000473:pathology*; D011014:Pneumonia / Q000276:immunology / Q000473:pathology* / Q000821:virology; D013447:Sulfites / Q000494:pharmacology
D000393:Air Pollutants; D016207:Cytokines; D016166:Free Radical Scavengers; D013447:Sulfites; D000171:Acrolein; C042345:hydrogen sulfite