INFLUENCE OF INTRAVENOUS N-3 LIPID SUPPLEMENTATION ON FATTY-ACID PROFILES AND LIPID MEDIATOR GENERATION IN A PATIENT WITH SEVERE ULCERATIVE-COLITIS

N-3 fatty acids were supplied to a 36-year-old female patient sufferin g from ulcerative colitis and severe steroid side-effects, in a sequen ce of parenteral and enteral administration. During a moderately activ e period of disease, 200 ml d(-1) fish oil-derived lipid emulsion (eic osapentaenoic acid [EPA], 4.2 g; docosahexaenoic acid [DHA], 4.2 g) wa s infused for 9 days, in parallel with rapid tapering of the steroid d ose. Disease activity declined rapidly, and the patient was subsequent ly provided with 16 fish oil capsules per day (EPA, 2.9 g; DHA, 1.9 g) for 2 months. At the end of this period of therapy, severe colitis re curred with intestinal and extraintestinal manifestations. The n-3 lip id emulsion was then used for intravenous alimentation (29 days, maxim um dose 300 ml per day); during this time, marked improvement of the i nflammatory bowel disease was noted. During both periods of parenteral n-3 lipid administration, total plasma EPA and DHA contents increased several-fold, surpassing that of arachidonic acid; this plasma n-3 fa tty acid enrichment was only maintained to a minor extent during the i ntermediate period of dietary fish oil supplementation. The intravenou sly administered EPA-containing triglycerides were rapidly hydrolyzed, as evidenced by the appearance of substantial quantities of EPA in th e plasma free fatty acid fraction. Platelet and neutrophil total membr ane content of EPA and DHA as well as n-3 fatty acid/AA membrane ratio s similarly increased during the periods of intravenous n-3 lipid admi nistration and declined during oral fish oil uptake. In contrast, eryt hrocyte membrane enrichment in EPA and DHA occurred only after the pro longed (2 month) period of dietary n-3 lipid supplementation. Ex vivo stimulation of neutrophils with A23187 showed progressive increase in 5-series leukotriene- and 5-HEPE-generation during both periods of n-3 lipid infusion, in parallel with the rise of plasma EPA contents. Max imum 5-series/4-series leukotriene ratios surpassed 0.25. Similarly, r atios of thromboxane B-3/B-2 liberated from ex vivo stimulated platele ts surpassed 0.4 during ongoing n-3 lipid infusion. The profound chang es in fatty acid profiles and lipid mediator generation may be related to the reduction in colitis activity observed during the periods of i ntravenous n-3 lipid supplementation.