Suppressive effect of docosahexaenoyl-lysophosphatidylcholine and 17-hydroxydocosahexaenoyl-lysophosphatidylcholine on levels of cytokines in spleen of mice treated with lipopolysaccharide

Lysophosphatidylcholine (lysoPC) with polyunsaturated fatty acyl chains has been known to be anti‐inflammatory in vivo. In the present study, we examined the effect of docosahexaenoyl‐lysophosphatidylcholine (DHE‐lysoPC) and 17‐hydroxydocosahexaenoyl‐lysophosphatidylcholine (17‐HDHE‐lysoPC) on spleen weight and cytokine level in spleen of mice treated with lipopolysaccharide (LPS). For this purpose, mice were administrated i.p. with DHE‐lysoPC or 17‐HDHE‐lysoPC 1 h before i.p. injection of LPS. First, DHE‐lysoPC (50–400 µg/kg) was found to suppress the LPS‐induced increase of spleen weight dose‐dependently, and such a suppressive effect was greater for 17‐HDHE‐lysoPC, compared to DHE‐lysoPC. Next, in an attempt to see the effect of DHE‐lysoPC on cytokine levels in spleen of mice treated with LPS, DHE‐lysoPC was found to suppress LPS‐induced increase in the levels of cytokines such as TNF‐α, IL‐1β, or IL‐6 in a dose dependent manner (50–400 µg/kg), in contrast to DHA showing a significant action at a high dose (400 µg/kg) only. The greater suppressive effect of 17‐HDHE‐lysoPC (15–150 µg/kg) than DHE‐lysoPC suggested that action of DHE‐lysoPC may be enhanced through lipoxygenation process. Presumably in support of this, when the interval time between 17‐HDHE‐lysoPC administration and LPS challenge was varied, the cytokine‐suppressing effect was found to be augmented in a time‐dependent manner. Taken all together, it is suggested that DHE‐lysoPC and 17‐HDHE‐lysoPC may be beneficial in suppressing the inflammation in spleen tissue. Structures of free DHA, DHA esterified in lysophosphatidylcholine, and C17‐hydroxylated DHA esterified in lysoPC.