Dietary beta-carotene supplementation modulates the production of tumour necrosis factor-alpha by human monocytes.

Abstract

Epidemiological studies have shown a strong inverse association between intake of the antioxidant carotenoid, 8-carotene, and the incidence of cancer [l]. The immune system plays a major role in cancer prevention and it has been suggested that 8-carotene might prevent carcinogenesis by enhancing immune cell activity [2]. Tumour necrosis factor-a (TNF), an immunostimulatory cytokine secreted by blood monocytes and tissue macrophages, has a selective toxic effect on a variety of malignant cells. Tumour regression in animal models, following local injection of 8carotene, is associated with an induction of TNF at the tumour site [3], and 8-carotene can increase the stimulated secretion of TNF by human monocytes in vitro[4]. Therefore, it is possible that one mechanism by which Bcarotene might inhibit tumour development in man is by enhancing the secretion of TNF by monocytes. We undertook a double-blind placebo-controlled crossover study to examine the effect of 8-carotene supplementation, given at a dietary achievable level, on the ex vivo stimulated secretion of TNF by human blood monocytes. Twenty-five healthy non-smoking males (age range 18-60 y. who were not taking regular medication or vitamin supplements) were randomly allocated into two groups. Following baseline 12 h-fasting blood sampling, participants in Group 1 were provided with 27 placebo capsules (containing vegetable oil) and instructed to consume one capsule per day; participants in Group 2 were given 27 identical capsules supplemented with B-carotene (15 mg, equivalent to eating 150 g carrots per day) and were similarly instructed. After a further fasting-blood sample was taken on Day 28 of the study, the participants were crossed onto the other capsules and a final blood sample was taken after a further 28 d. Blood monocytes were purified by density centrifugation (over NycoPrep 1.063; Nycomed, Birmingham) [5], adjusted to 2 x 106 cells/ml in RPMI-1640 (supplemented with 5% FCS and antibiotics) and incubated for 24 h in the absence or presence of LPS (10 pg/ml) to stimulate TNF secretion. The cells were then sedimented and the concentration of TNF present in the supernatants was quantified by ELISA (R&D Systems, Oxon).