Carcinogenesis, Vol. 20, No. 8, 1471-1476,
August 1999
© 1999 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
Immunomodulatory action of citrus auraptene on macrophage functions and cytokine production of lymphocytes in female BALB/c mice
First Department of Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293,
1 Department of Health and Physical Education, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502-8585,
2 Department of Hygiene, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8076,
3 Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501,
4 Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Wakayama 649-6433 and
5 Department of Food Science and Technology, Faculty of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8224, Japan
The modifying effects of auraptene isolated from the peel of citrus fruit (Citrus natsudaidai Hayata) on macrophage and lymphocyte functions were investigated in mice. Female BALB/c mice were gavaged with auraptene at a dose of 100, 200 or 400 mg/kg once a day for 10 consecutive days. Glucose consumption of peritoneal macrophages was significantly higher than that in the control group (P < 0.05–0.001) in auraptene-treated mice at all doses at 24, 48 and 72 h incubation except for mice given 200 mg/kg auraptene at 24 h incubation. Activity of acid phosphatase in peritoneal macrophages was significantly increased in mice treated with auraptene at a dose level of 100 mg/kg (P < 0.001). Activity of ß-glucuronidase in peritoneal macrophages in the auraptene-treated mice at all doses was significantly higher than that in the control group (P < 0.001), but there was no significant difference in lactate dehydrogenase activity of peritoneal macrophages at any dose. Interleukin (IL)-1ß production of peritoneal macrophages in the auraptene-treated mice at all doses was significantly higher than that in the control group (P < 0.05–0.001). Tumor necrosis factor 
production of peritoneal macrophages in mice gavaged with auraptene at a dose of 200 mg/kg was significantly higher than that in the control group (P < 0.05). Auraptene did not affect proliferation of spontaneous splenic lymphocytes in mice at any dose. Stimulation indices in mice given auraptene at a dose of 200 mg/kg were significantly higher than that in the control group (P < 0.05). When spleenic lymphocytes were cultured without concanavalin A (Con A), IL-2 and interferon (IFN) 
productions were not detectable in the supernatant. However, IL-2 and IFN production stimulated by Con A were significantly increased in mice gavaged with auraptene at dose levels of 100 and 200 mg/kg (P 0.05–0.001). Auraptene did not enhance spontaneous IL-4 production by splenocytes. There was no significant difference in IL-4 production of splenic lymphocytes stimulated by Con A in all groups. These findings might suggest that oral administration of citrus auraptene effectively enhanced macrophage and lymphocyte functions in mice.
Abbreviations: APH, acid phosphatase; Con A, concanavalin A; GLU, ß-glucuronidase; IFN, interferon; IL, interleukin; LDH, lactate dehydrogenase; LPS, lipopolysaccharide; NK, natural killer; PEC, peritoneal exudate cells; SI, stimulation index; TGF, tumor growth factor; Th, T helper; TNF, tumor necrosis factor.
6 To whom correspondence should be addressed Email: takutt{at}kanazawa-med.ac.jp
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