DIETARY N-3 FATTY-ACIDS DIFFERENTIALLY AFFECT SICKNESS BEHAVIOR IN MICE DURING LOCAL AND SYSTEMIC INFLAMMATION

We tested the hypothesis that increased dietary fish oil levels (via m odulation of the production of inflammatory mediators) modulate sickne ss symptoms (i.e., anorexia, cachexia, fever, lethargy) of systemic an d local inflammation. Swiss Webster mice were implanted with bioteleme ters to measure body temperature and motor activity and were fed a die t high in n-3 fatty acids (17% wt/wt menhaden oil) or a reference diet (17% wt/wt hydrogenated coconut oil or normal rodent chow) for 6 wk. Local inflammation was induced by subcutaneous injection of turpentine (100 mu l/mouse). Systemic inflammation was elicited by intraperitone al injection of lipopolysaccharide (LPS; 2.5 mg/kg). Fever, lethargy, anorexia, and weight decrease during turpentine abscess were all inhib ited (P < 0.05) in mice fed the fish oil diet. Indomethacin, similar t o the fish oil diet, attenuated the turpentine-induced symptoms in mic e fed a normal diet. Dietary n-3 fatty acids prevented fever and atten uated the decrease in body weight caused by LPS but did not affect the LPS-induced lethargy and anorexia. Within 90 min of LPS injection, th e bioactivity of plasma tumor necrosis factor-alpha (TNF-alpha) increa sed to 98.2 +/- 5.1 ng/ml in mice fed fish oil compared with 32.6 +/- 3.6 ng/ml in those fed the reference diet (P < 0.05). Plasma prostagla ndin E(2) (PGE(2)) levels after LPS injection of mice fed the control diet increased within 90 min to 16.4 +/- 5.1 pg/ml. Mice fed the fish oil diet did not show any elevation in plasma PGE(2) levels at that ti me (P < 0.05). We speculate that dietary n-3 fatty acids suppressed PG E(2)-related responses, including a PGE(2)-dependent negative feedback on TNF-alpha production, which resulted in differential modulation of sickness behavior depending on the locus of inflammation.