EFFECTS OF N-(4-HYDROXYPHENYL)-RETINAMIDE ON THE NUMBER AND CYTOTOXICITY OF NATURAL-KILLER-CELLS IN VITAMIN-A-SUFFICIENT AND VITAMIN-A-DEFICIENT RATS

N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid with antic arcinogenic activity, has been shown to lower the plasma retinol level rapidly and significantly. We reported previously that vitamin A-defi cient rats (plasma retinol <0.175 mu mol/l) have a low number of natur al killer (NK) cells in peripheral blood. To investigate the effects o f 4-HPR on NK cell number and activity, two studies were conducted. In study 1, vitamin-A-sufficient rats were fed a 'therapeutic' dose of 4 -HPR (2 mmol/kg of diet) for 30 days. Despite a low plasma retinol con centration (approximately 0.1 mu mol/l), the number of NK cells was no t reduced. Moreover, the NK cytolytic activity per cell was significan tly elevated. White blood cell and differential counts were normal. In study 2, the biological activity of 4-HPR was examined in vitamin-A-d eficient rats. Rats depleted of vitamin A were fed a diet containing 4 -HPR (54.7 mu g/g of diet) for 11 days. Vitamin-A-dependent processes including growth, hematocrit, lymphocyte count and the number of NK ce lls were restored. For comparison, another group of vitamin-A-deficien t rats were repleted with retinoic acid (RA; 4.2 mu g/g diet); this tr eatment also effectively restored these vitamin-A-dependent processes. Therefore, despite the plasma-retinol-lowering property of 4-HPR, tre atment with this retinoid did not impair NK cell number or function. I ndeed, 4-HPR showed vitamin A activity similar to RA, and may stimulat e NK cell cytotoxicity.