Distribution and Immune Responses Resulting from Oral Administration of D-Limonene in Rats

Abstract

We investigated the relationship between the absorptive pathway and the immune responses of the lung, particularly the phagocytic function of alveolar macrophages (MO) 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 out-put 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 Mφ, in which there was frequently a focal exu-dation of lipid droplets containing D-limonene into the alveolar cavity through alveolar cap-illary walls. Second, D-limonene orally given to rats (250, 500, 1, 000mg/kg/d) for 8 con-secutive days resulted in a marked increase in both the number and the phagocytic activity of alveolar Mφ compared to the controls. BALF from rats dosed with D-limonene (1, 000mg/kg/d) enhanced the phagocytic activity of alveolar Mφ from control rats because the dose was prolonged. The activity of alveolar Mφ 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 Mφ there, or indirectly activates it through activated lymphocytes.