Biology Reference
In-Depth Information
IFN- is more marked after peripheral administration and is believed to be due to
the secondary release of cytokines such as IL-1. Additionally, interferons are potent
inducers of somnolence and fever, and it has been suggested that these neurobehavioral
responses also contribute to the observed reduction in feeding. IL-6 is a major inducer
of the acute phase response and has a direct central inhibitory effect on feeding.
However, this effect is less marked than that of IL-1, interferons, or TNF-, suggest-
ing that IL-6 plays a contributory role in cytokine-induced anorexia rather than being
a major mediator. Studies have shown that low doses of IL-1 administered centrally
mainly affect meal size and duration but not frequency, whereas higher doses affect
all feeding parameters. The effects appear to be specific, as they are blocked by co-
administration of IL-1 receptor antagonist (IL-1ra)
[30]
.
Cytokines cause anorexia by peripheral humoral mechanisms as well as direct
action on the hypothalamus
[31,32]
. Although subdiaphragmatic vagotomy can atten-
uate the effects of peripheral LPS or IL-1 on fever, reduced social exploration, taste
aversion, and other aspects of sickness behavior, there is little evidence for a major
role of the vagus in anorexia
[33]
. There is some evidence that the anorexic effects
of cytokines may be secondary to the release of cholecystokinin (CCK), glucagon,
and insulin in the periphery
[32]
. IL-1 increases circulating CCK and decreases food
intake and gastric emptying. However, recent evidence
[34]
indicates that the CCK
A
receptor antagonist, devazepide, did not block the anorectic action of IL-1, thus fail-
ing to support a role for CCK in IL-1-induced anorexia. Nevertheless, the effect of
IL-1 in delaying gastric emptying is antagonized by the central administration of a
CRH receptor antagonist
[35]
.
Although cytokines may not be the sole factors responsible for the anorexia and
weight loss noted in pathological conditions, it is interesting that effects on feed-
ing and body weight are present in disorders involving chronic dysfunction of the
immune system, such as cancer, AIDS, and inflammatory bowel disease. In humans,
nausea and anorexia often accompany cytokine treatment, and patients with anorexia
nervosa have been found to have one or more factors in their sera that can stimulate
cytokine production.
12.2.4 Cytokines and Anhedonia
Experiments have also been undertaken to study the relationship between sickness
and hedonic processes. Hedonism in animals is commonly assessed through prefer-
ence and/or consumption of sweet solutions. The effects of LPS have been assessed
on taste reactivity patterns in rats (specific tongue and mouth movements) to thresh-
old and standard concentrations of saccharine, sucrose, and quinine. Reactivity pat-
terns to quinine and sucrose were unaffected by LPS. A standard concentration of
quinine (0.1 mM) evoked the same degree of aversion, and sucrose (90 mM) the
same intensity of hedonic reaction, as they did in the absence of LPS. However, LPS
altered the reactivity pattern to saccharine, in that treated rats showed fewer inges-
tive and more aversive responses to a standard (5 mM) concentration of saccharine
compared with controls. (At a threshold concentration of saccharine, the responses of
LPS- and saline-treated rats did not differ.) Although the results of this study support
