[[ International Symposium�F05 ]]

N-3 vs N-6 POLYUNSATURATED FATTY ACIDS (PUFA) IN CRITICAL ILLNESS Tsuguhiko Tashiro, M.D., H. Yamamori, N. Hayashi, K. Furukawa, Y. Morishima, T. Sugiura, T. Itabashi, W. Sano, Y. Toyoda, H. Nitta, J. Hirano, K. Nishiya and N. Nakajima, M.D. Department of Surgery, Chiba University School of Medicine

The effects of n-6 and n-3 PUFA on protein metabolism, cell-mediated immunity, and production of cytokines and prostanoids were studied in experimental animals and patients with esophageal cancer. EXPERIMENTAL STUDY (1) EFFECTS OF N-3 AND N-6 FAT EMULSION ON STRESS RESPONSE IN BURNED RATS After 2 weeks of oral fat-free diet, 40 SD rats were divided into 4 TPN groups. Group "N6-B(+)"(n=10): TPN with safflower oil emulsion (20% of total energy), group "N3-B(+)"(n=10): TPN with safflower oil (19% of total energy) and structured EPA and DHA (2:1) emulsion (1% of total energy). "Control-B(+)"(n=10) and "Control-B(-)" (N=10) received fat-free TPN. After 7 days of TPN, "N6-B(+)", "N3-B(+)" and "Control-B(+)" were subjected to 20% full-thickness scald burns, but "Control-B(-)" were not. On the second day of subjecting the rats to the burn, urinary excretion of catecholamine (UCA) and Nitrogen balance (NB) were measured. Delayed type hypersensitivity (DTH) was assessed by the ear thickness response to Dinitrofluorobenzene. Serum IL-6, IL-8, IL-10, TNF�� PGE2 and TXB2 were also measured by EIA. Group "N6-B(+)" demonstrated increased UCA, serum IL-6 and TNF��p��0.05), and decreased NB (p��0.05) by burn injury, when compared with "Control-B(+)". But in "N3-B(+)", TNF��and IL-10 were reduced(p��0.05), and NB was improved (p��0.05). Suppressed DTH induced by burn injury, which was not influenced by n-6 PUFA, was significantly improved by the administration of n-3 PUFA, when compared with "Control-B(+)" and "N6-B(+)". (2) EFFECTS OF FISH OIL EMULSION ON ENDOTOXIN TRANSLOCATION IN BURNED RATS Using the same experimental model, 36 rats were divided into 4 TPN groups. Group "G" was fed by fat-free TPN. Group "SO" received safflower oil emulsion, "FO" received fish oil emulsion and "SO/FO" received the mixture of safflower and fish oil emulsion (1:1) which supplied 20% of total energy. Then, rats were subjected to burns and were sacrificed in the same manner as previous study. Serum PGE2, TXB2 and fatty acids profile were measured. The endotoxin content in liver and spleen were measured by ENDOSPASY. Serum EPA increased dose dependently. PGE2 and TXB2 increased in "SO", but not significantly. Endotoxin translocation tended to increase in "SO", and significantly decreased in "FO" when compared with "SO". (3) CELL-MEDIATED IMMUNITY AND SERUM GM-CSF ARE DEPENDENT ON DOSE OF N-3 PUFA Forty-three rats were divided into 5 TPN groups including safflower oil (SO) and/or fish oil (FO) fat emulsion providing 20% of total energy. The control group was fed by fat-free TPN. The content of fish oil(%)/safflower oil(%) of other 4 groups were 0/20, 4/16, 10/10 and 20/0. Serum IL-6, IL-8, GM-CSF, PGE2, TXB2 and fatty acids profile were analyzed. DTH was also assessed. DTH, GM-CSF and EPA content increased proportionately with the intravenous dose of fish oil emulsion. GM-CSF correlated significantly with DTH (r=0.316, p��0.04). No differences of IL-6, IL-8, PGE2, and TXB2 were observed among the groups. CLINICAL STUDY (1) EFFECTS OF INTRALIPID AND ORAL ENTERAL EPA ON POSTOPERATIVE CYTOKINE PRODUCTION AND LYMPHOCYTES FUNCTION ACCORDING TO THE SEVERITY OF SURGICAL STRESS Seven patients who underwent gastrectomy (moderately stressed group, "G-gl") and 6 who underwent esophagectomy (severely stressed group, "E-gl") were fed by fat-free TPN. Nineteen gastrectomized ("G-fat") and 6 esophagectomized ("E-fat") patients were fed by TPN with Intralipid (20%. of total energy). EPA methyl ester (1.8g/day) were administered orally or enterally to the patients who received TPN with Intralipid ("E-EPA", n=7). IL-6 was measured at 1, 2, 6, 12 hours and 3, 7 days after their operations. CRP, ConA and PHA stimulated lymphocyte proliferation, NK activity and CD4/8 were also determined. In group "E-fat", the serum IL-6 significantly increased at 2 and 6 hours after operation (p��0.05) and postoperative immunity tended to be suppressed, when compared with "E-gl". Cell-mediated immune function was suppressed postoperatively in both "E" groups, and the suppression tended to be greater in "E-fat" rather than in "E-gl". In the patients who underwent gastrecomy, postoperative serum IL-6 was significantly lower and postoperative immunosuppression was not observed when compared with the esophagectomized patients. No significant differences of IL-6, CRP, and cell-mediated immune function between "G-fat" and "G-gl" were observed. Oral/enteral supplementation of EPA methyl ester (group "E-EPA") significantly reduced the postoperative IL-6 production (p��0.05 at I , 2 and 6 hours after operation), and improved cell-mediated immune function 3 weeks after operation (p=0.05). (2) EFFECTS OF ENTERAL EPA ON IMMUNE FUNCTION DURING THE POSTOPERATIVE CHEMO-RADIATION THERAPY IN PATIENTS WHO UNDERWENT OPERATION FOR ESOPHAGEAL CANCER The effects of enteral EPA on immune function during the postoperative chemo-radiation therapy were studied in patients who underwent operation for esophageal cancer. CBDCA and 5FU were administered with radiation (2Gy/day for 25 days) postoperatively. ConA and PHA stimulated lymphocyte proliferation, NK activity and CD418 were improved significantly during the chemo-radiation therapy in the patients fed enterally with EPA methyl ester (n=5), when compared with the patients without EPA (n=14). CONCLUSION N-6 PUFA amplified, and n-3 PUFA reduced the stress response and immunosuppression induced by burn injury or surgical stress. N-3 PUFA is potentially beneficial for the critically ill patients.