Interactions of beta-carotene and flavonoids on the secretion of pro-inflammatory mediators in an in vitro system.

Chronic inflammation, a process linked to increased oxidative stress, may induce many diseases. Whether beta-carotene prevents inflammation is unclear. Using phorbol-12-myristate-13-acetate (PMA)-stimulated HL-60 cells, we investigated the effects of 2 or 20 microM beta-carotene on the inflammatory reaction of monocyte/macrophage-like cells and the modulation of 20 microM quercetin or naringenin, two flavonoids, of the effects of beta-carotene. The effects of quercetin and naringenin were compared with that of alpha-tocopherol, a well-known antioxidant. The stimulated HL-60 cells were also co-incubated with A549 cells to investigate the DNA-damaging ability of the stimulated monocyte/macrophage-like cells on target cells. Our results showed that preincubation with 20 microM beta-carotene significantly enhanced the release of two pro-inflammatory mediators, interleukin-8 and tumor necrosis factor-alpha, in PMA-stimulated HL-60 cells and slightly increased the DNA-damaging ability of these cells. By contrast, 2 microM beta-carotene had an inhibitory effect on the inflammatory reaction in PMA-stimulated cells. The higher dose of beta-carotene also exerted pro-inflammatory effects in lipopolysaccharide-stimulated RAW264.7 cells. Furthermore, quercetin, naringenin, and alpha-tocopherol partly suppressed the pro-inflammatory effects of 20 microM beta-carotene on PMA-stimulated HL-60 cells, and the suppressing effects of quercetin and naringenin were better than or similar to those of alpha-tocopherol. Quercetin also additively or synergistically enhanced the inhibitory effects of 2 microM beta-carotene on the secretion of pro-inflammatory mediators and the DNA-damaging ability of PMA-stimulated HL-60 cells. The mechanisms underlying the effect of the flavonoids were associated with their antioxidant activity and inhibition of the production of pro-inflammatory cytokines. Our results urge consideration of the safety of beta-carotene supplementation concerning effects on inflammation and suggest that the interaction between beta-carotene and quercetin or naringenin may alter the effects of beta-carotene on the secretion of pro-inflammatory mediators.