Abstract
Acute respiratory infections are an important health concern. Traditionally, polysaccharide-enriched extracts from plants, containing immunomodulatory rhamnogalacturonan-I (RG-1), were used prophylactically. We established the effects of dietary supplementation with carrot-derived RG-I (cRG-I, 0–0.3–1.5 g/day) in 177 healthy individuals (18–65 years) on symptoms following infection with rhinovirus strain 16 (RV16). Primary outcomes were changes in severity and duration of symptoms, and viral load in nasal lavage. Secondary outcomes were changes in innate immune and anti-viral responses, reflected by CXCL10 and CXCL8 levels and cell differentials in nasal lavage. In a nested cohort, exploratory transcriptome analysis was conducted on nasal epithelium. Intake of cRG-I was safe, well-tolerated and accelerated local cellular and humoral innate immune responses induced by RV16 infection, with the strongest effects at 1.5 g/d. At 0.3 g/d, a faster interferon-induced response, induction of the key anti-viral gene EIF2AK2, faster viral clearance, and reduced symptom severity (−20%) and duration (−25%) were observed. Anti-viral responses, viral clearance and symptom scores at 1.5 g/d were in between those of 0 and 0.3 g/d, suggesting a negative feedback loop preventing excessive interferon responses. Dietary intake of cRG-I accelerated innate immune and antiviral responses, and reduced symptoms of an acute respiratory viral infection.
Highlights
Acute respiratory infections (ARI) are an important health concern and common colds alone account for 150 million workdays missed by employees in the US, with an economic impact of more than $20 billion annually [1]
Double-blind, placebo-controlled trial, we investigated the effect of carrot rhamnogalacturonan-I (cRG-I) at 0 g/day, 0.3 g/day [21,22,23,24,25,26] and 1.5 g/day, and we used a validated WURSS-21 questionnaire to evaluate the dose-effect of cRG-I on the symptom scores and duration of symptoms following a standardized ARI triggered by exposure to rhinovirus strain 16 (RV16) in healthy subjects
Post-hoc analysis using a pharmacokinetic model indicated that symptoms reduced to 50% (“symptom elimination half-life”, t1/2 ) at day 6.5 in the no-dose group, whereas this was at day 4.7 (−28%) for the low-dose group and day 6.1 (−5%)
Summary
Acute respiratory infections (ARI) are an important health concern and common colds alone account for 150 million workdays missed by employees in the US, with an economic impact of more than $20 billion annually [1]. ARI are a major source of morbidity and mortality in patients with inflammatory airway disease, elderly and newborns [2,3] Can condition airways for severe secondary infections [4], and emerging respiratory viruses can lead to life-threatening disease, as exemplified by influenza infections and recently by the SARS-Cov pandemic [5]. Most ARI resolve within one to two weeks and the host response is driven to a large extent by the innate immune system. Innate immune responses are triggered by signaling via pattern-recognition receptors (PRR) such as Toll-like receptors (TLR), double-strand. PRR funnel their signals into interactions with regulated signaling cascades, which initiate the key antiviral interferon response as well as other common anti-viral and innate immune responses [8,9]
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