Dietary n-3 fatty acids differentially affect sickness behavior in
mice during local and systemic inflammation.
Kozak, Wieslaw, Dariusz Soszynski, Karin Rudolph, Carole A. Conn,
Matthew J. Kluger.
Institute for Basic and Applied Medical Research, The Lovelace
Institutes, 2425 Ridgecrest Dr. SE, Albuquerque, New Mexico 87108,
USA
APStracts 3:0422R, 1996.
Kozak, Wieslaw, Dariusz Soszynski, Karin Rudolph, Carole A. Conn, and
Matthew J. Kluger. Dietary n-3 fatty acids differentially affect
sickness behavior in mice during local and systemic inflammation.
American Journal of Physiology (Regulatory Integrative Comp.
Physiol.). We tested the hypothesis that increased dietary fish oil
(due to modulation of the production of inflammatory mediators)
modulates sickness symptoms (i.e., anorexia, cachexia, fever,
lethargy) to 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% w/w
menhaden oil) or reference diets (17% w/w hydrogenated coconut oil or
normal rodent chow) for 6 weeks. Local inflammation was induced by
subcutaneous injection of turpentine (100 ml/mouse). Systemic
inflammation was elicited by injecting lipopolysaccharide (LPS; 2.5
mg/kg; ip injection). Fever, lethargy, anorexia and decrease in
weight during turpentine abscess were all inhibited (p<0.05)
in mice fed fish oil diet. Indomethacin, similar to fish oil diet,
attenuated the turpentine-induced symptoms in mice fed normal diet.
Dietary n-3 fatty acids prevented fever and attenuated drop in body
weight due to LPS, but did not affect the LPS-induced lethargy and
anorexia. Within 90 min of LPS injection bioactivity of plasma TNF-a
increased to 98.2 5.1 ng/ml in mice fed fish oil versus 32.6 3.6
ng/ml in those fed reference diet (p<0.05). Plasma PGE2 level
after LPS injection of mice fed control diet increased within 90 min
to 16.4 5.1 pg/ml. Mice fed fish oil diet did not show any elevation
in plasma PGE2 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-a production, which resulted
in differential modulation of sickness behavior depending on the
locus of inflammation.
Received 24 July 1996; accepted in final form 5 November 1996.0
APS Manuscript Number R436-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996