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 modulation of the production of inflammatory mediators) modulate sickness symptoms (i.e., anorexia, cachexia, fever, lethargy) of systemic and local inflammation. Swiss Webster mice were implanted with biotelemeters to measure body temperature and motor activity and were fed a diet 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 microl/mouse). Systemic inflammation was elicited by intraperitoneal injection of lipopolysaccharide (LPS; 2.5 mg/kg). Fever, lethargy, anorexia, and weight decrease during turpentine abscess were all inhibited (P < 0.05) in mice fed the fish oil diet. Indomethacin, similar to the fish oil diet, attenuated the turpentine-induced symptoms in mice fed a normal diet. Dietary n-3 fatty acids prevented fever and attenuated the decrease in body weight caused by LPS but did not affect the LPS-induced lethargy and anorexia. Within 90 min of LPS injection, the bioactivity of plasma tumor necrosis factor-alpha (TNF-alpha) increased 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 prostaglandin E2 (PGE2) 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 PGE2 levels at that time (P < 0.05). We speculate that dietary n-3 fatty acids suppressed PGE2-related responses, including a PGE2-dependent negative feedback on TNF-alpha production, which resulted in differential modulation of sickness behavior depending on the locus of inflammation.
Kozak
W
W
Institute for Basic and Applied Medical Research, The Lovelace Institutes, Albuquerque, New Mexico 87108, USA.
Soszynski
D
D
Rudolph
K
K
Conn
C A
CA
Kluger
M J
MJ
D000818:Animals; D000855:Anorexia; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia; D000074263:Coconut Oil; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D005334:Fever; D005395:Fish Oils; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010938:Plant Oils; D012894:Sleep Stages; D013997:Time Factors; D014425:Turpentine
D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D008070:Lipopolysaccharides; D010938:Plant Oils; C033266:Menhaden oil; D000074263:Coconut Oil; D014425:Turpentine; D007213:Indomethacin