Abstract
BackgroundSmokers have increased susceptibility and altered innate host defense responses to influenza virus infection. Broccoli sprouts are a source of the Nrf2 activating agentsulforaphane, and short term ingestion of broccoli sprout homogenates (BSH) has been shown to reduce nasal inflammatory responses to oxidant pollutants.ObjectivesAssess the effects of BSH on nasal cytokines, virus replication, and Nrf2-dependent enzyme expression in smokers and nonsmokers.MethodsWe conducted a randomized, double-blind, placebo-controlled trial comparing the effects of BSH on serially sampled nasal lavage fluid (NLF) cytokines, viral sequence quantity, and Nrf2-dependent enzyme expression in NLF cells and biopsied epithelium. Healthy young adult smokers and nonsmokers ingested BSH or placebo (alfalfa sprout homogenate) for 4 days, designated Days -1, 0, 1, 2. On Day 0 they received standard vaccine dose of live attenuated influenza virus (LAIV) intranasally. Nasal lavage fluids and nasal biopsies were collected serially to assess response to LAIV.ResultsIn area under curve analyses, post-LAIV IL-6 responses (P = 0.03) and influenza sequences (P = 0.01) were significantly reduced in NLF from BSH-treated smokers, whileNAD(P)H: quinoneoxidoreductasein NLF cells was significantly increased. In nonsmokers, a similar trend for reduction in virus quantity with BSH did not reach statistical significance.ConclusionsIn smokers, short term ingestion of broccoli sprout homogenates appears to significantly reduce some virus-induced markers of inflammation, as well as reducing virus quantity. Nutritional antioxidant interventions have promise as a safe, low-cost strategy for reducing influenza risk among smokers and other at risk populations.Trial RegistrationClinicalTrials.gov NCT01269723
Highlights
Influenza virus infection is a serious, large-scale global public health problem
Using transient low-level nasal infection with standard dose of live attenuated influenza virus (LAIV) vaccine as a model, we have previously shown that healthy young adult smokers have blunted host defense responses to LAIV and enhanced viral replication, compared to healthy nonsmokers [10]
Pilot study To confirm that our broccoli sprout homogenate (BSH)
Summary
Influenza virus infection is a serious, large-scale global public health problem. Current vaccines and antiviral drugs are only partially effective against influenza, and may be ineffective in the setting of epidemics due to antigenic shift or emergence of drugresistant strains [1,2]. Using transient low-level nasal infection with standard dose of live attenuated influenza virus (LAIV) vaccine as a model, we have previously shown that healthy young adult smokers have blunted host defense responses to LAIV and enhanced viral replication, compared to healthy nonsmokers [10]. We have shown that epithelial antiviral responses to influenza in vivo and in experimental cell culture models are blunted in smokers, and that the abnormalities can be corrected in vitrowith antioxidants including sulforaphane(SFN) [11,12,13]. Smokers have increased susceptibility and altered innate host defense responses to influenza virus infection. Broccoli sprouts are a source of the Nrf activating agentsulforaphane, and short term ingestion of broccoli sprout homogenates (BSH) has been shown to reduce nasal inflammatory responses to oxidant pollutants
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