DAILY SUPPLEMENTATION WITH MAXEPA SUPPRESSES ENDOTOXIN-INDUCIBLE MONOCYTIC PROCOAGULATION IN DOGS

Fish intake has long been recognized to play an important role in huma n health, for example, in reduction of the incidence of heart disease and some cancers and as immunosuppressors. In this study, we examined the effect of dietary supplementation with fish oils (FO) on monocytic procoagulant activity (PCA) in dogs. Six mongrel dogs were fed daily chow containing FO concentrate (MaxEPA, 0.5 g/kg body wt/day) for 8 we eks. Blood samples were drawn during a 20-week experimental period [i. e., before, during (weekly), and after (biweekly) MaxEPA supplementati on] to measure monocytic PCA, PCA activation induced by endotoxin [lip opolysaccharide (LPS)], and plasma levels of total cholesterol, trigly ceride, and fibrinogen (FBG;). PCA was generally stimulated drasticall y by approximately 19-fold on incubation of whole blood with LPS (1 mu g/ml) in vitro for 2 hr. The basal PCA remained essentially unchanged over the entire experimental period irrespective of MaxEPA supplement ation; however, LPS-induced PCA activation was reduced by 50% (P < 0.0 5) 3 weeks after MaxEPA was introduced. This inhibition remained signi ficant up to Week 10 and reached 75% at Week 12. Thereafter, PCA activ ation gradually returned to the level before supplementation. The plas ma levels of total cholesterol, triglyceride, and fibrinogen were dete rmined to be 178.8 +/- 6.0, 46.7 +/- 3.9, and 61.3 +/- 5.5 mg/dl, resp ectively. These plasma contents were neither correlated with LPS-induc ed PCA activation nor affected significantly by MaxEPA supplementation . Following a similar protocol, we also showed that MaxEPA supplementa tion resulted in a profound depression (-80%) of LPS-induced PCA activ ation in a rabbit, and PCA activation was eventually restored after re moval of MaxEPA from the diet, Our results suggest a beneficial potent ial of MaxEPA supplementation in the management of atherothrombotic di seases in response to LPS infection. (C) 1997 Academic Press.