Abstract
Carotenoids are part of the human diet and a regular low-dose intake of these compounds from natural sources is normally preferred. Carotenoid supplementation in various diseases, including cancer, was described to be useful, but evidence has been obtained that high-dose supplementation of β-carotene may be unsafe, especially to smokers and asbestos-exposed workers, because of a stastically detected increased cancer risk. The negative effect might be mediated by carotenoid breakdown products having a high reactivity towards biomolecules. It has been suggested that these compounds originate from nonenzymatic cleavage of carotenoids by oxidants liberated in large amounts by neutrophils that accumulate in various inflammatory diseases and, in particular, in pulmonary disorders characterized by profound abnormalities in inflammatory pathways, such as those triggered by tobacco smoking. Carotenoid breakdown products, in turn, may affect neutrophil response in different ways that depend on the concentration that is reached by these products in the medium. In vitro studies show that nanomolar and micromolar concentrations of carotenoid derivatives stimulate superoxide production by neutrophils activated by phorbol myristate acetate (PMA), while a slight inhibition is noticed with cells activated by the chemotactic tripeptide N-formyl-Met-Leu-Phe (f-MLP). At higher concentrations, carotenoid breakdown products inhibit superoxide production in the presence of both PMA and f-MLP. 
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