Auteur(s) : D. Arsenijevic, I. Garcia, C. Vesin, D. Vesin, Y. Arsenijevic, J. Seydoux, L. Girardier, B. Ryffel, A. Dulloo, D. Richard, Department of Pathology, CMU, 1, rue Michel-Servet, CH 1211 Geneva 4.
Illustrations
Figure 1 A. Absolute level of energy expenditure (EE) in response to lipopolysaccharide
(LPS) injection in control (negative littermates) and sTNFR1-IgG transgenic
mice 2 hours before and 4 hours after injection.
Results are expressed in W/mouse (means ± SE); n = 20 in each group.
Note that in transgenic mice, the increase in metabolic rate was about
50% of that in controls. B. EE of the same mice measured 2 days
after LPS injection at the same time of day. C and D. Body
weight (C) and food intake (D) before and in response to
LPS injection over a period of 12 days. Data are expressed in g. day
-1.mouse -1 (means ± SE), n = 16 in each group.
Food intake recovered more rapidly in transgenic mice.
Figure 2 Energy expenditure (A) and food intake (B) in response to LPS injection
in wild-type (control), sTNFR1-IgG, TNF-alpha KO, LT-alpha KO, anti-IFN-gamma,
IFN-gamma R KO mice and in anti-asialo, GM1 antibody-treated mice.
A. Normalised EE for body weight to power 0.75 (to adjust for
differences in body weight) and expressed as the ratio of 4 hours post-injection
over pre-injection values (means ± SE); n = 12 for control and 6-8
for other groups of mice. Compared to control, increases of EE in all
groups are significantly less (p ¾ 0.03). B. Food intake in
g.day- 1.mouse- 1 of the same groups of mice, expressed
as ratio of 2 day post-injection over pre-injection values (means ±
SE). Food intake recovery after LPS is significantly higher in IFN-gamma
deficient mice, indicating that this cytokine is involved in LPS anorexia.
Figure 3 Kinetics of serum cytokine concentrations in response
to LPS injection in control and sTNFR1-IgG transgenic mice.
TNF-alpha (A) and IL-6 (B) were determined by bioassay,
whereas IL-1beta (C) and IFN-gamma (D) were measured by
immunoassay as described in Materials and methods and are expressed either
in pg/ml or in ng/ml; n = 6 in each group.
Figure 4 mRNA expression of TNF-alpha, IL-1beta and IL-6 in
spleen (A) and brain (B) in response to LPS, determined 90 min or day
2 post-injection in control and sTNFR1-IgG transgenic mice; cytokine mRNAs
were normalised to beta-actin mRNA levels; n = 3 in each group.
Whereas expressions of these cytokines are significantly induced, although
to a lesser extent (p ¾ 0.05) in the spleen of transgenic mice, they
are not detected in their brains.
Figure 5 Blood-brain barrier permeability as determined 90 min after LPS
administration by retro-orbital injection of Evans blue dye or with phosphate-buffered
saline (PBS) in wild type and sTNFR1-IgG transgenic mice; n = 3 in each
group.
A marked Evans blue accumulation indicates increased blood-brain barrier
permeability, and was measured spectrophotometrically (OD: optical density).
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