Distribution and immune responses resulting from oral administration of D-limonene in rats

J Nutr Sci Vitaminol (Tokyo). 2002 Apr;48(2):155-60. doi: 10.3177/jnsv.48.155.


We investigated the relationship between the absorptive pathway and the immune responses of the lung, particularly the phagocytic function of alveolar macrophages (Mphi) after oral administration of D-limonene in rats. D-Limonene was orally administered in oily solution with a stomach tube in thoracic duct-cannulated rats, and the lymphatic output of D-limonene was measured. D-Limonene levels reached a maximum in thoracic duct lymph and lung 3 h after its oral administration. It also significantly increased in bronchoalveolar lavage fluid (BALF) and alveolar Mphi, in which there was frequently a focal exudation of lipid droplets containing D-limonene into the alveolar cavity through alveolar capillary walls. Second, D-limonene orally given to rats (250, 500, 1,000 mg/kg/d) for 8 consecutive days resulted in a marked increase in both the number and the phagocytic activity of alveolar Mphi compared to the controls. BALF from rats dosed with D-limonene (1,000 mg/kg/d) enhanced the phagocytic activity of alveolar Mphi from control rats because the dose was prolonged. The activity of alveolar Mphi following in vitro incubation with D-limonene also increased in a dose-dependent manner. An oral administration of D-limonene enhanced the Con A-stimulated proliferation of splenocytes. These results suggest that D-limonene taken up from the thoracic duct lymph moves to the lung and directly activates the immune response of alveolar MO there, or indirectly activates it through activated lymphocytes.

MeSH terms

  • Absorption
  • Administration, Oral
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology*
  • Cyclohexenes
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Immunologic
  • Gas Chromatography-Mass Spectrometry
  • Limonene
  • Lung / metabolism
  • Lymphocyte Activation / drug effects
  • Macrophages, Alveolar / immunology*
  • Male
  • Phagocytosis / drug effects*
  • Random Allocation
  • Rats
  • Rats, Inbred F344
  • Specific Pathogen-Free Organisms
  • Terpenes / administration & dosage*
  • Terpenes / immunology
  • Terpenes / pharmacokinetics
  • Thoracic Duct / metabolism


  • Cyclohexenes
  • Terpenes
  • Limonene