Advertisement

The effect of β-carotene supplementation on the immune function of blood monocytes from healthy male nonsmokers

      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Although there is strong epidemiologic evidence that diets rich in carotenoids such as β-carotene are associated with a reduced incidence of cancer, the cellular mechanisms underlying this phenomenon remain unknown. This article describes the effect of dietary β-carotene supplementation on both the expression of functionally associated surface molecules on human monocytes and on the secretion of the cytokine tumor necrosis factor-α (TNF-α) by monocytes, all of which are involved in the initiation and regulation of immune responses involved in tumor surveillance. A double-blind, placebo-controlled, crossover study was undertaken in which 25 healthy, adult male nonsmokers were randomly assigned to receive β-carotene (15 mg daily) or placebo for 26 days, followed by the alternative treatment for a further 26 days. The expression of functionally related monocyte surface molecules was quantified by flow cytometry, and ex vivo secretion of TNF-α was quantified by an enzyme-linked immunosorbent assay, before and after each treatment period. After dietary supplementation there were significant increases in plasma levels of β-carotene and in the percentages of monocytes expressing the major histocompatibility complex class II molecule HLA-DR and the adhesion molecules intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. In addition, the ex vivo TNF-α secretion by blood monocytes was significantly increased after supplementation. These findings suggest that moderate increases in the dietary intake of β-carotene can enhance cell-mediated immune responses within a relatively short period of time, providing a potential mechanism for the anticarcinogenic properties attributed to β-carotene.

      Abbreviations:

      FITC (fluorescein isothiocyanate), HLA (human leukocyte antigen), HEPES (N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid), HPLC (high-performance liquid chromatography), ICAM-1 (intercellular adhesion molecule-1), LFA (leukocyte function-associated antigen), MEM (minimal essential medium), MHC (major histocompatibility complex), PUFA (polyunsaturated fatty acid), TNF-α (tumor necrosis factor-α)
      To read this article in full you will need to make a payment

      References

        • Byers T
        • Perry G
        Dietary carotenes, vitamin C, and vitamin E as protective antioxidants in human cancers.
        Annu Rev Nutr. 1992; 12: 139-159
        • Peto R
        • Doll R
        • Buckley JD
        • Sporn MB
        Can dietary beta-carotene materially reduce human cancer rates?.
        Nature. 1981; 290: 201-208
        • The Alpha-Tocopherol Beta-Carotene Cancer Prevention Study Group
        The effect of vitamin E and beta-carotene on the incidence of lung cancer and other cancers in male smokers.
        N Engl J Med. 1994; 330: 1029-1035
        • Bendich A
        Beta-carotene and the immune response.
        in: 4th ed. Proc Nutr Soc. 50. 1991: 263-274
        • Chandra RK
        Nutrition and the immune system.
        in: 4th ed. Proc Nutr Soc. 52. 1993: 77-84
        • Unanue ER
        • Cerottini J-C
        Antigen presentation.
        FASEB J. 1989; 3: 2496-2502
        • Bach FH
        Class II genes and products of the HLA-D region.
        Immunol Today. 1985; 6: 89-94
        • Janeway CA
        • Bottomly K
        • Babich J
        • et al.
        Quantitative variation in Ia antigen expression plays a central role in immune regulation.
        Immunol Today. 1984; 5: 99-104
        • Springer TA
        Adhesion receptors of the immune system.
        Nature. 1990; 346: 425-434
        • Simpson JR
        • Hoffman-Goetz L
        Nutritional deficiencies and immunoregulatory cytokines.
        in: Cunningham-Rundles S Nutrient modulation of the immune response. Marcel Dekker Inc, New York1993: 31-45
        • Hamblin AS
        Cytokines and cytokine receptors.
        Oxford University Press, Oxford, England1993
        • Fiers W
        Tumor necrosis factor.
        in: Characterization at the molecular, cellular and in vivo level. 4th ed. FEBS Lett. 285. 1991: 199-212
        • Abdel-Fatth G
        • Watzl B
        • Huang D
        • Watson RR
        Beta-carotene in vitro stimulates tumor necrosis factor alpha and interleukin 1-alpha secretion by human peripheral blood mononuclear cells.
        Nutr Res. 1993; 13: 863-871
        • Hart DJ
        • Scott KJ
        Development and evaluation of an HPLC method for the analysis of carotenoids in foods, and the measurement of the carotenoid content of vegetables and fruits commonly consumed in the UK.
        Food Chem. 1995; 54: 101-111
        • Finglas PM
        • Bailey A
        • Walker A
        • Loughridge JM
        • Wright AJA
        • Southon S
        Vitamin C intake and plasma ascorbic acid concentration in adolescents.
        Br J Nutr. 1993; 69: 563-576
        • Miwa H
        • Yamamoto M
        Liquid chromatographic determination of free and total fatty acid in milk and milk products as their 2-nitrophenylhydrazines.
        J Chromatogr. 1990; 523: 235-246
        • Hughes DA
        • Townsend PJ
        • Haslam PL
        Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis.
        Clin exp Immunol. 1992; 87: 279-286
        • Hughes DA
        • Pinder AC
        • Piper Z
        • Johnson IT
        • Lund EK
        Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes.
        Am J Clin Nutr. 1996; 63: 267-272
        • Pinder AC
        • Purdy PW
        • Poulter SAG
        • Clark DC
        Validation of flow cytometry for rapid enumeration of bacterial concentrations in pure cultures.
        J Applied Bacteriol. 1990; 69: 92-100
        • Altman DG
        Practical statistics for medical research.
        Chapman and Hall, London1991
        • Prabhala RH
        • Garewal HS
        • Hicks MJ
        • Sampliner RE
        • Watson RR
        The effects of 13-cis-retinoic acid and beta-carotene on cellular immunity in humans.
        Cancer. 1991; 67: 1556-1560
        • Fuller CJ
        • Faulkner H
        • Bendich A
        • Parker RS
        • Roe DA
        Effect of beta-carotene supplementation on photosuppression of delayed-type hypersensitivity in normal young men.
        Am J Clin Nutr. 1992; 56: 684-690
        • Khan IU
        • Boehm KD
        • Elmets CA
        Modulation of interferon-gamma-induced HLA-DR expression on the human keratinocyte cell line SCC-13 by ultraviolet radiation.
        Photochem Photobiol. 1993; 57: 285-290
        • Tang A
        • Udey MC
        Inhibition of epidermal Langerhans cell function by low dose ultraviolet B radiation.
        in: Ultraviolet B radiation selectively modulates ICAM-1 (CD54) expression by murine Langerhans cells. 4th ed. J Immunol. 146. 1991: 3347-3355
        • Mathews-Roth MM
        Beta-carotene: clinical aspects.
        in: Spiller GA Scala J New protective roles for selected nutrients. Alan R. Liss Inc, New York1989: 17-38
        • Greenwald ED
        • Greenwald ES
        Skin cancer.
        in: Cancer epidemiology. Medical Examination Publishing Co. Inc, New York1983: 26-29
        • Bogden JD
        • Bendich A
        • Kemp FW
        • et al.
        Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people.
        Am J Clin Nutr. 1994; 60: 437-447
        • Bianchi-Santamaria A
        • Fedeli S
        • Santamaria L
        Short communication: possible activity of beta-carotene in patients with the AIDS related complex.
        Med Oncol Tumor Pharmacother. 1992; 9: 151-153
        • Shklar G
        • Schwartz J
        Tumor necrosis factor in experimental cancer regression with alphatocopherol, beta-carotene, canthaxanthin and algae extract.
        Eur J Cancer Clin Oncol. 1988; 24: 839-850
        • van Poppel G
        • Kok FJ
        • Hermus RJJ
        Beta-carotene supplementation in smokers reduces the frequency of micronuclei in sputum.
        Br J Cancer. 1992; 66: 1164-1168
        • Micozzi MS
        • Brown ED
        • Edwards BK
        • et al.
        Plasma carotenoid response to chronic intake of selected foods and β-carotene supplements in men.
        Am J Clin Nutr. 1992; 55: 1120-1125
        • Gruner S
        • Volk H-D
        • Falck P
        • Baehr RV
        The influence of phagocytic stimuli on the expression of HLA-DR antigens: role of reactive oxygen intermediates.
        Eur J Immunol. 1986; 16: 212-215
        • Snyder DS
        • Beller DI
        • Unanue ER
        Prostaglandins modulate macrophage Ia expression.
        Nature. 1982; 299: 163-165
        • Kunkel SL
        • Wiggins RC
        • Chensue SW
        • Larrick J
        Regulation of macrophage tumor necrosis factor production by prostaglandin E2.
        Biochem Biophys Res Commun. 1986; 137: 404-410
        • Kunkel SL
        • Spengler M
        • May MA
        • Spengler R
        • Larrick J
        • Remick D
        Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression.
        J Biol Chem. 1988; 263: 5380-5384
        • Halevy O
        • Sklan D
        Inhibition of arachidonic acid oxidation by β-carotene, retinol and a-tocopherol.
        Biochim Biophys Acta. 1987; 918: 304-307