An immune-shift induced by lycopene; from an eosinophil-dominant type towards an eosinophil/neutrophil-co-dominant type of airway inflammation

Abstract

Lycopene as the main carotenoid from tomatoes is known to have beneficial effects on various inflammatory diseases. In mice, lycopene ameliorates asthma symptoms and in human asthmatic patients serum lycopene levels are reduced. To further investigate the immunomodulatory effect of lycopene, first, we used a ragweed pollen extract (RWE)-induced asthma model in mice. In a second approach, we established a RWE-induced asthma model in gerbils, because of a more human-like carotenoid absorption in these animals. In RWE-sensitized/RWE-challenged gerbils (C+) following a basal diet, mainly the number of eosinophils in the broncho-alveolar lavage (BAL) significantly increased, comparable to RWE-sensitized/PBS-challenged gerbils (C−). In RWE-sensitized/PBS-challenged gerbils with lycopene-supplementation (L−), an elevated number of mainly neutrophils, in addition to eosinophils, was detected compared to C−, whereas in RWE-sensitized/RWE-challenged animals with lycopene-supplementation (L+), mainly increased neutrophil numbers in BAL were detected compared to C+. Furthermore, using LC-MS, we determined an array of eicosanoids/docosanoids in the lungs and observed that 5-, 8-lipoxygenase (LOX) and cyclooxygenase (COX) pathways were significantly increased after intranasal RWE-challenge in sensitized mice and just by tendency in gerbils. In PBS- and RWE-challenged animals, lycopene-supplementation significantly raised COX-pathway metabolites. In conclusion, we found that lycopene-supplementation resulted in an increased inflammatory influx of neutrophils in combination with increased COX-pathways metabolites. This pro-inflammatory, pro-neutrophil activity induced by lycopene might be an important shift from allergic asthma towards an inflammatory symptomatic asthma type, though with the potential for resolution.