| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
, LPS, and MDP
1 Institute for Animal Sciences, Physiology and Animal Husbandry, Swiss Federal Institute of Technology, 8092 Zurich, Switzerland; and 2 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
 |
ABSTRACT |
|---|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
We investigated the extrinsic gut neural
mediation of the suppression of food intake in male Sprague-Dawley rats
induced by peripheral intraperitoneal administration of 2 µg/kg
interleukin-1
(IL-1), 100 µg/kg bacterial
lipopolysaccharide (LPS), and 2 mg/kg muramyl dipeptide (MDP). Food
intake during the first 3 and 6 h of the dark cycle was measured in
rats with subdiaphragmatic vagal deafferentation
(n = 9), celiac superior mesenteric
ganglionectomy (n = 9), combined
vagotomy and ganglionectomy (n = 9),
and sham deafferentation (n = 9).
IL-1, LPS, and MDP suppressed food intake at 3 and 6 h in all
surgical groups. The results demonstrate that neither vagal nor
nonvagal afferent nerves from the upper gut are necessary for the
feeding-suppressive effects of intraperitoneal IL-1, LPS, or MDP in
the rat and suggest that peripheral administration of immunomodulators
produces anorexia via a humoral pathway.
interleukin-1; lipopolysaccharide; muramyl dipeptide; food
intake; brain-gut communication; cytokine; bacterial products
| |
INTRODUCTION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
A REDUCTION OF FOOD INTAKE is a prominent component of
the host's acute phase response to bacterial infection (10). The bacterial products lipopolysaccharide (LPS) and muramyl dipeptide (MDP)
trigger the acute phase response and may be involved in the
accompanying hypophagia, because peripheral administration of both LPS
and MDP reduces food intake (16). In addition, these bacterial products
promote the synthesis and release of the immunomodulatory cytokine
interleukin (IL)-1, which also suppresses feeding (16).
Although the neural and/or humoral mediation of the
feeding-suppressive effects of peripheral administration of these
compounds is unclear, a role for subdiaphragmatic vagal afferent fibers in the hypophagia produced by bacterial products and cytokines has been
suggested from studies evaluating the effects of surgical transection
of the vagus nerve. For example, subdiaphragmatic vagotomy, which
nonselectively transects all gut vagal sensory and motoneurons,
attenuated the ability of intraperitoneally injected LPS and IL-1 to
suppress instrumental lever pressing for food in mice (2).
Subdiaphragmatic vagotomy has also been shown to inhibit a variety of
other effects of peripheral LPS and IL-1, such as LPS-stimulated
fever (33), LPS-induced central c-fos expression (32), IL-1-induced
depression in social exploration (1), and IL-1-induced hyperalgesia
(35). However, more recent work from our group demonstrated that
selective subdiaphragmatic vagal rootlet deafferentation, eliminating
primarily vagal sensory traffic between the gut and the brain, failed
to attenuate the suppression of solid food intake induced by
peripherally administered LPS or IL-1 (29).
The sensory component of the subdiaphragmatic vagus nerve is not the
only extrinsic neural pathway that could mediate the feeding
suppression produced by peripheral administration of these agents. The
sympathetic celiac-superior mesenteric ganglion complex is the main
neuroanatomic pathway through which splanchnic, nonvagal visceral
afferents flow from the upper gastrointestinal tract to the central
nervous system (CNS). Systemic administration of IL-1 and LPS alters
the efferent outflow in renal, splenic, and adrenal sympathetic nerves
in rats (14, 20), suggesting that these compounds may also activate
splanchnic visceral afferents that signal CNS sites controlling
feeding. Thus nonvagal, splanchnic afferents may mediate the hypophagic
effects of bacterial products and IL-1.
The present study used subdiaphragmatic vagal deafferentation, nonvagal
visceral deafferentation by celiac-superior mesenteric ganglionectomy,
and a combination of these two surgical procedures to further elucidate
the roles of subdiaphragmatic vagal and nonvagal visceral afferents in
the suppression of food intake produced by peripherally administered
IL-1, LPS, and MDP.
| |
METHODS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
Male Sprague-Dawley rats (Biological Research Laboratories) initially weighing 220-250 g were used in the experiment. They were individually housed in a temperature-controlled (22 ± 2°C) colony room, in stainless steel drawer cages with wire bottoms. The rats were maintained on an artificial 12:12-h light-dark cycle with the lights on from 2200 to 1000. Water was available ad libitum. Rats were deprived of food and water for 16 h before surgery. They were anesthetized by intraperitoneal injection (1.00 ml/kg body wt) with a mixture of 80 mg/ml ketamine (Ketasol-100, Graub), 20 mg/ml xylazine (Rompun, Bayer), and 0.05 mg/ml acepromazine (Sedaline, Chassot and Cie). Supplemental injections of this mixture were administered as necessary to maintain a surgical level of anesthesia. Body temperature was monitored and maintained at 36-37°C throughout all surgical procedures with an electric heating pad.
Animals were ranked by weight and divided into four surgical groups, distributing equivalent body weights in each group as closely as possible before the four surgeries: subdiaphragmatic vagal deafferentation (SDA, n = 9), celiac superior mesenteric ganglionectomy (CGX, n = 9), combined vagotomy and ganglionectomy (COM, n = 9), and sham deafferentation (Sham, n = 9). The vagal deafferentation procedures were performed according to the procedure of Norgren and Smith (24). The deafferentation procedure consisted of a left afferent vagal rootlet transection at the brain stem level and a contralateral subdiaphragmatic vagotomy of the dorsal trunk. The left afferent vagal rootlet transection cut all of the vagal afferents arising from the common hepatic, accessory celiac, and ventral gastric branches as they entered the brain stem, leaving all of the vagal efferent fibers in these branches intact. This is possible in the rat because the vagus diverges into discrete sensory and motor bundles as it enters the caudal brain stem. The dorsal vagal subdiaphragmatic vagotomy was performed according to the procedure of Smith et al. (30). This unilateral vagotomy disconnected all subdiaphragmatic vagal afferents and efferents from the dorsal vagal trunk, which supplies the dorsal gastric and celiac branches. For the CGX, the stomach and spleen were exposed and gently retracted and held in place with warm saline-soaked gauze. The descending aorta was visualized, and the celiac-superior mesenteric ganglion complex was isolated (9) with fine forceps, severed from the splanchnic nerve trunks with fine scissors, and then completely surgically excised. The adjacent celiac and superior mesenteric arteries were not damaged during the procedure. Finally, during the sham surgeries, the left vagus, as it penetrates the posterior foramen of the skull, was exposed but left untouched, and a midline laparotomy and exposure of the dorsal subdiaphragmatic trunk were made, leaving the trunk intact.
Solid food intake measurements.
Behavioral testing began 1 wk after the completion of the surgical
procedures. Three studies were performed. In each study, all rats
received a single intraperitoneal injection of drug or corresponding
vehicle solution between 20 and 5 min before lights out at 1000. The
order of drug and vehicle treatments was counterbalanced between the 2 test days for each surgical group, in which five rats of each surgical
group received the drug on the first test day and the other four rats
of each group received the drug treatment on the second test day. Each
test day was separated by at least 1 intervening day, during which
injections of drug or vehicle were not made. In the first study, rats
received a single intraperitoneal injection of 2 µg/kg recombinant
human IL-1 (R & D Systems) (dissolved in sterile physiological
saline containing 2.0 µg BSA/10 µl) or BSA-saline vehicle delivered
in 0.1 ml/100 g rat. In the second study, rats received a single
intraperitoneal injection of 100 µg/kg LPS [from
Escherichia coli serotype 0111:B4,
Sigma (St. Louis, MO) L-2630, dissolved in sterile saline] or
saline vehicle injection delivered in 0.1 ml/100 g rat. In the third
study, rats received a single intraperitoneal injection of 2 mg/kg MDP
(adjuvant peptide, Sigma A-9519, dissolved in sterile saline) or a
saline vehicle injection delivered in 0.1 ml/100 g rat. The doses of IL-1, LPS, and MDP were selected on the basis of previous studies comparing the effectiveness of these compounds to suppress food intake
in rats (16, 17). At the beginning of each test, just before lights
out, food containers with ground rat chow diet (Nafag) were placed in
the cages. Food intake was measured by manually weighing (±0.1 g)
the feeding cups at 3 and 6 h after the onset of the dark cycle at
1000. Spillage was collected on paper spread beneath the cages and was
also measured at 3- and 6-h time points.
Functional vagotomy verification. Previous studies have demonstrated that left vagal afferent rootlet transection combined with dorsal vagal subdiaphragmatic transection blocks the suppression of feeding produced by low (1-6 µg/kg) but not higher (8-16 µg/kg) intraperitoneal doses of the brain-gut peptide cholecystokinin (CCK) (23, 30). To obtain a functional verification of the vagal deafferentation procedures in the present study, consumption of the ground rat chow diet was measured in the animals of each group 30 min after lights out at 1000. The rats received a single intraperitoneal injection of 4 µg/kg CCK or saline vehicle solution delivered in 0.1 ml/100 g rat body wt between 10 and 5 min before lights out at 1000. The order of the drug and vehicle treatments was counterbalanced between the 2 test days for each group as previously described. Again, each test day was separated by at least 1 intervening day, during which injections of drug or vehicle were not made. Water was available ad libitum at all times.
Histological vagotomy verification. All rats were killed between 6-7 wk postsurgery for histological verification of vagotomies to minimize the possibility of functional regeneration of the vagus nerves (T. L. Powley, personal communication). To verify the subdiaphragmatic vagal deafferentations in the SDA and SDA-CGX animals, we used a fluorescent tracer strategy (27). Briefly, immediately after the completion of all behavioral food intake tests, each animal received two intraperitoneal injections (0.5 ml) of fluorogold (Fluorochrome) solution (2 mg/ml of saline). Three days after the fluorogold injections, rats were anesthetized with a mixture of ketamine and xylazine and perfused with three solutions into the left ventricle. The first solution consisted of 250 ml of PBS with 0.2 ml of heparin (1,000 U/ml) delivered over a period of 15 min. The second solution contained 500 ml of 4% paraformaldehyde dissolved in PBS, followed by 200 ml of 20% sucrose in 4% paraformaldehyde.
For SDA and COM rats, the fixed brain was exposed and examined in situ under microscopic observation (×20) to verify that the vagal afferent rootlets were 1) cut on the left side and 2) intact on the right side as they entered the medulla. The brain and brain stem were then removed and cryoprotected in 20% sucrose in PBS. The medulla was blocked and sectioned at 40 µm on a sliding microtome. Sections for the fluorogold analysis were thaw mounted on slides, air dried, dehydrated by clearing in alcohols and xylene, and placed under a coverslip with DPX (Aldrich, Milwaukee, WI). Fluorogold label in the brain stem was examined with a Zeiss (Thornwood, NY) epifluorescence microscope. Because fluorogold is taken up and transported retrogradely in intact neurons but not in neurons with transected axons, a successful dorsal trunk subdiaphragmatic vagotomy was confirmed by 1) the absence of label in the right dorsal motor vagal nucleus, where the cut dorsal subdiaphragmatic vagal trunk would project, and 2) the presence of label in the left dorsal motor vagal nucleus, where the intact efferents of the ventral vagal subdiaphragmatic trunk project (27). Additional confirmation of the dorsal subdiaphragmatic vagotomy was also made by microscopic inspection and localization of the silk sutures around the cauterized dorsal vagal nerve trunks, with no visible fibers in between the proximal and distal stumps. With use of these verification procedures, all SDA and COM rats were determined to have successful, complete vagal deafferentations. Verification of splanchnic nerve section and celiac-superior mesenteric ganglionectomy was performed postsurgically by examining the descending aorta at the region between the branch points between the celiac and superior mesenteric arteries. The complete absence of any neural and lymphatic tissue surrounding these vessels indicated a successful transection in all cases. This verification procedure is consistent with the neuroanatomic pathway taken by splanchnic afferents en route to the upper gut (9).Data analyses. Differences between group means were analyzed using separate two-way repeated-measures ANOVA at each of the time points, followed by a Student-Newman-Keuls test when appropriate. P values <0.05 were considered significant.
| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
IL-1.
IL-1 (2 µg/kg) significantly inhibited food intake in every
surgical group at 3 and 6 h [3 h overall
F(3,32) = 43.6, P < 0.001; 6 h overall
F(3,32) = 79.47, P < 0.001] (Fig.
1). There was no significant interaction
between surgical group and drug effect at either 3- or 6-h time points
[3 h F(3,32) = 0.378, P > 0.75; 6 h
F(3,32) = 1.961, P > 0.15]. At each time point,
food intake after saline vehicle administration did not differ
significantly across surgical groups [3 h
F(3,57) = 2.265, P > 0.08; 6 h
F(3,57) = 4.47, P < 0.007]. There
was also no significant difference between the surgical groups in the
reduced food intake induced by IL-1 at 3 h
[F(3,57) = 0.676, P > 0.57]. However, IL-1
administration resulted in a greater suppression of food intake in CGX
rats (P < 0.01) compared with the
SDA and Sham rats at 6 h (Fig. 1).
|
LPS. LPS (100 µg/kg) significantly inhibited food intake in every surgical group at 3 and 6 h [3 h overall F(3,32) = 60.6, P < 0.001; 6 h overall F(3,32) = 125.2, P < 0.001] (Fig. 2). There was no significant interaction between surgical group and drug effect at either 3- or 6-h time points [3 h F(3,32) = 0.423, P > 0.73; 6 h F(3,32) = 0.59, P > 0.6]. At each time point, food intake after saline vehicle administration did not differ significantly across surgical groups [3 h F(3,57) = 0.543, P > 0.65; 6 h F(3,57) = 1.37, P > 0.25]. There were also no significant differences between the surgical groups in the reduced food intake induced by LPS at each time point [3 h F(3,57) = 1.3, P > 0.25; 6 h F(3,57) = 0.89, P > 0.45].
|
MDP. MDP (2 mg/kg) significantly inhibited food intake in every surgical group except SDA [3 h overall F(3,32) = 47.5, P < 0.001] (Fig. 3) and in all surgical groups at 6 h [overall F(3,32) = 125.2, P < 0.001] (Fig. 3). There was no significant interaction between surgical group and drug effect at either 3- or 6-h time points [3 h F(3,32) = 0.855, P > 0.45; 6 h F(3,32) = 0.51, P > 0.6]. At each time point, food intake after saline vehicle administration did not differ significantly across surgical groups [3 h F(3,57) = 0.924, P > 0.4; 6 h F(3,57) = 0.48, P > 0.69].
|
CCK. During the 30-min feeding trial, CCK (4 µg/kg) significantly reduced food intake in Sham-operated rats but not in SDA or COM rats [overall F(2,24) = 6.64, P < 0.005] (Fig. 4). COM and SDA rats did not differ statistically in their lack of feeding suppression in response to CCK (P < 0.05).
|
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
The present results replicate our previous finding that
subdiaphragmatic vagal afferents are not necessary for the
feeding-suppressive effects of intraperitoneal IL-1 and LPS and
extend those findings to include another bacterial cell wall compound,
MDP. Our functional test of complete subdiaphragmatic vagal
deafferentation confirmed in both SDA and COM groups that low doses of
CCK (4 µg/kg) failed to suppress food intake. Furthermore, these data
reveal that neither splanchnic nor vagal subdiaphragmatic visceral
afferents are necessary to mediate the hypophagia produced by
intraperitoneal administration of IL-1, LPS, or MDP, because
combined subdiaphragmatic vagal deafferentation and celiac-superior
mesenteric ganglionectomy failed to alter the ability of these
compounds to suppress feeding.
The present finding that subdiaphragmatic vagal afferent fibers are not
required for the hypophagic effect of intraperitoneal IL-1, LPS, or
MDP is consistent with results from other studies showing that intact
vagal afferent fibers are not required to mediate several other effects
of peripheral immunomodulator administration. For instance, hepatic
branch vagotomy fails to attenuate intravenous IL-1
and
intraperitoneal LPS-induced anorexia in rats (17, 19). In guinea pigs,
the febrile response to intramuscular injection of MDP is not
significantly altered by subdiaphragmatic vagotomy (7). Furthermore,
systemic treatment with capsaicin fails to reverse LPS- and
IL-1-induced instrumental bar pressing for food in rats and mice
(3).
Results from studies involving complete subdiaphragmatic vagotomy,
which nonselectively transects all subdiaphragmatic vagal sensory and
motor fibers, have demonstrated that the intact vagus contributes to a
wide range of the behavioral and neural effects of peripheral IL-1
and LPS administration, including hyperthermia, hyperalgesia, and
food-motivated behavior (28, 34). Unlike the present study, previous
work evaluating the role of the intact vagus in food intake measured
instrumental food-motivated behavior rather than actual food intake,
making it difficult to compare results across such experiments. In
addition, differences between the ineffectiveness of the SDA
preparation in this study and the ability of total subdiaphragmatic
vagotomy to attenuate feeding-related responses to LPS and IL-1 in
other studies may be due in part to the fact that SDA spares one-half
of the vagal efferent supply of the gut, whereas total subdiaphragmatic
vagotomy transects all subdiaphragmatic vagal afferents and efferents.
These contrasting vagotomy procedures may produce important differences in the metabolic context in which immunomodulators act to suppress food intake. In the present study, the SDA procedure results in transient weight loss with complete recovery of body weight to sham control levels within 1 wk and subsequent maintenance of normal body weight gain. This is in contrast to the more long-lasting effects of total subdiaphragmatic vagotomy, which are characterized by more severe initial weight loss and a failure to subsequently reach the body weights achieved by sham-operated control rats postsurgically (15). More severe and prolonged body weight loss may reduce the anorectic potential of peripherally administered immunomodulators.
The design of this study reflects the fact that the vagus nerve is not
the only afferent gut-brain pathway potentially involved in
immunomodulator-induced feeding suppression. Nonvagal, splanchnic afferents might also mediate the hypophagic effects of
immunomodulators, secondary to the ability of these compounds to
stimulate sympathetic efferent outflow. LPS administration in rats
increases the expression of c-fos protein in discrete brain nuclei in
regions that mediate sympathetic outflow to sympathetic preganglionic
neurons in the spinal cord (31), and systemic administration of IL-1
and LPS alters sympathetic efferent outflow in rats (14, 20, 21). Despite these demonstrations, surgical transection of the
celiac-superior mesenteric ganglion complex failed to attenuate
IL-1-, LPS-, and MDP-induced hypophagia, indicating that such
changes in sympathetic efferent outflow are not necessary for the
hypophagic response to these compounds. The previously reported failure
of combined pharmacological - and -adrenergic receptor blockade
by phentolamine and propanolol to attenuate LPS-induced hypophagia (16)
is consistent with this interpretation.
Gut enteric neuronal function is also influenced by cytokine exposure;
IL-1 inhibits acetylcholine release and stimulates norepinephrine
release in isolated rat small intestinal myenteric plexus (12, 22).
However, the present results demonstrate that any potential
feeding-suppressive effects of this type of immunomodulator-induced
enteric activation do not require either intact vagal or splanchnic
afferents.
Finally, IL-1 administration resulted in a greater suppression of
food intake in CGX rats compared with SDA and Sham rats at 6 h (Fig.
1). Because celiac-superior mesenteric ganglionectomy not only
transects splanchnic gut visceral afferents but also transects gut
sympathetic efferents, CGX may eliminate a sympathetic influence that
limits the feeding-suppressive effects of IL-1 but is only evident
when vagal afferents are present. The nature of this signal remains to
be identified.
Perspectives
The inability of selective vagal deafferentation, CGX, or a combination of both surgical procedures to attenuate the hypophagia induced by peripherally administered IL-1, LPS, and MDP demonstrates that these
compounds can act on the CNS to suppress feeding via humoral pathways.
Peripherally synthesized cytokines may enter the CNS
1) by crossing the blood-brain
barrier (BBB) during infection, when LPS increases BBB permeability
(11), 2) through the
circumventricular organs that lack a BBB, or
3) by specific transport mechanisms (4). Once available to the CNS, cytokines
1) have potent anorectic effects and
2) may induce the local production
of anorexic cytokines in the CNS (26). Intracerebroventricular
injection of pathophysiological levels of several cytokines, including
IL-1 and tumor necrosis factor (TNF)-, decreases food intake in
rats (25). In addition, humoral access to cytokines or LPS may
stimulate endothelial cells at the BBB to produce eicosanoids or other
messengers that act on the CNS to suppress ingestion (4). Finally,
peripheral immunomodulators may stimulate the production of peripheral
humoral signals related to energy balance and food intake. Studies in
hamsters (8) and humans (13) have demonstrated that the administration
of LPS or TNF and IL-1 increases
1) the expression of mRNA for leptin in adipose tissue and/or 2)
plasma levels of leptin, which have been correlated with decreases in
food intake (8). Furthermore, IL-1 mediates the ability of
peripheral LPS to induce leptin during inflammation (5). However, it
has been reported that intraperitoneal LPS causes anorexia in both
ob/ob
and
db/db
mice (6), which lack functional leptin and functional leptin receptors, respectively. Although these data suggest that a functioning leptin signaling pathway is not critical for the feeding-suppressive actions
of peripheral LPS, LPS also stimulates increases in plasma cytokines
that may act via the other humoral mechanisms described above.
Together, these data suggest that progress in understanding the
anorexic actions of peripheral immunomodulators will come through
systematic, comprehensive evaluation of these putative humoral
pathways.
| |
ACKNOWLEDGEMENTS |
|---|
This work was supported by Swiss Federal Institute of Technology Grant 020-096-95 and National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-47208.
| |
FOOTNOTES |
|---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests: G. J. Schwartz, Dept. of Psychiatry and Behavioral Sciences, Johns Hopkins Univ. School of Medicine, 720 Rutland Ave., Ross Rm. 618, Baltimore, MD 21205.
Received 9 February 1998; accepted in final form 8 April 1998.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Methods
Results
Discussion
References
|
|---|
1.
Bluthé, R. M.,
B. Michaud,
K. W. Kelley,
and
R. Dantzer.
Vagotomy blocks behavioral effects of interleukin-1 injected via the i.p. route but not via other systemic routes.
Neuroreport
7:
2823-2827,
1996[Medline].
2.
Bret-Dibat, J. L.,
R. M. Bluthé,
S. Kent,
K. W. Kelley,
and
R. Dantzer.
Lipopolysaccharide and interleukin-1 depress food-motivated behavior in mice by a vagal-mediated mechanism.
Brain Behav. Immun.
9:
242-246,
1995[Medline].
3.
Bret-Dibat, J. L.,
C. Creminon,
J. Y. Couraud,
K. W. Kelley,
R. Dantzer,
and
S. Kent.
Systemic capsaicin pretreatment fails to block the decrease in food motivated behavior induced by lipopolysaccharide and interleukin-1.
Brain Res. Bull.
42:
443-449,
1997[Medline].
4.
Dantzer, R.
How do cytokines say hello to the brain? Neural versus humoral mediation.
Eur. Cytokine Netw.
5:
271-273,
1994[Medline].
5.
Faggioni, R.,
G. Fantuzzi,
J. Fuller,
C. A. Dinarello,
K. R. Feingold,
and
C. Grunfeld.
IL-1 mediates leptin induction during inflammation.
Am. J. Physiol.
274 (Regulatory Integrative Comp. Physiol. 43):
R204-R208,
1998
6.
Faggioni, R.,
J. Fuller,
A. Moser,
K. R. Feingold,
and
C. Grunfeld.
LPS-induced anorexia in leptin deficient (ob/ob) and leptin receptor-deficient (db/db) mice.
Am. J. Physiol.
273 (Regulatory Integrative Comp. Physiol. 42):
R181-R186,
1997
7.
Goldbach, J. M.,
J. Roth,
and
E. Zeisburger.
Fever suppression by subdiaphragmatic vagotomy in guinea pigs depends on the route of pyrogen administration.
Am. J. Physiol.
272 (Regulatory Integrative Comp. Physiol. 41):
R675-R681,
1997
8.
Grunfeld, C.,
C. Zhao,
J. Fuller,
A. Pollock,
A. Moser,
J. Friedman,
and
K. R. Feingold.
Endotoxin and cytokines induce the expression of leptin, the ob gene product, in hamsters.
J. Clin. Invest.
97:
2152-2157,
1996[Medline].
9.
Hamer, D. W.,
and
R. M. Santer.
Anatomy and blood supply of the celiac-superior mesenteric ganglion complex of the rat.
Anat. Embryol. (Berl.)
162:
353-362,
1981[Medline].
10.
Hart, B. L.
Biological basis of the behavior of sick animals.
Neurosci. Biobehav. Rev.
12:
123-137,
1988[Medline].
11.
Hickey, W. F.,
B. L. Hsu,
and
H. Kimura.
T-lymphocyte entry into the central nervous system.
J. Neurosci. Res.
28:
254-260,
1991[Medline].
12.
Hurst, S.,
and
S. M. Collins.
Interleukin-1 modulation of norepinephrine release from rat myenteric nerves.
Am. J. Physiol.
264 (Gastrointest. Liver Physiol. 27):
G30-G35,
1993
13.
Janik, J. E.,
B. D. Curti,
R. V. Considine,
H. C. Rager,
G. C. Powers,
W. G. Alvord,
J. W. Smith,
B. L. Gause,
and
W. C. Kopp.
Interleukin 1 increases serum leptin concentration in humans.
J. Clin. Endocrinol. Metab.
82:
3084-3086,
1997
14.
Kannan, H.,
Y. Tanaka,
T. Kunitake,
Y. Ueta,
T. Hayashida,
and
H. Yamashita.
Activation of sympathetic outflow by recombinant human interleukin-1 in conscious rats.
Am. J. Physiol.
270 (Regulatory Integrative Comp. Physiol. 39):
R479-R485,
1996
15.
Kraly, F. S.,
C. Jerome,
and
G. P. Smith.
Specific postoperative syndromes after total and selective vagotomies in the rat.
Appetite
7:
1-17,
1986[Medline].
16.
Langhans, W.
Bacterial products and the control of ingestive behavior: clinical implications.
Nutrition
12:
303-315,
1996[Medline].
17.
Langhans, W.,
R. Harlacher,
G. Balkowski,
and
E. Scharrer.
Comparison of the effects of bacterial lipopolysaccharide and muramyl dipeptide on food intake.
Physiol. Behav.
47:
805-813,
1990[Medline].
18.
Langhans, W.,
D. Salvodelli,
and
S. Weingarten.
Comparison of the feeding responses to bacterial lipopolysaccharide and interleukin-1.
Physiol. Behav.
53:
643-649,
1993[Medline].
19.
Laviano, A.,
Z. J. Yang,
M. M. Meguid,
M. Koseki,
and
J. L. Beverly.
Hepatic vagus does not mediate IL-1 induced anorexia.
Neuroreport
6:
1266-1268,
1995.
20.
MacNeil, B. J.,
A. H. Jansen,
A. H. Greenberg,
and
D. M. Nance.
Activation and selectivity of sympathetic nerve electrical activity response to bacterial endotoxin.
Am. J. Physiol.
270 (Regulatory Integrative Comp. Physiol. 39):
R264-R270,
1996
21.
MacNeil, B. J.,
A. H. Jansen,
L. J. Janz,
A. H. Greenberg,
and
D. M. Nance.
Peripheral endotoxin increases splenic sympathetic nerve activity via central prostaglandin synthesis.
Am. J. Physiol.
273 (Regulatory Integrative Comp. Physiol. 42):
R609-R614,
1997
22.
Main, C.,
P. Blennerhassett,
and
S. M. Collins.
Human recombinant interleukin-1 suppresses acetylcholine release from rat myenteric plexus.
Gastroenterology
104:
1648-1654,
1993[Medline].
23.
Moran, T. H.,
A. R. Baldessarini,
C. F. Salorio,
T. Lowery,
and
G. J. Schwartz.
Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin.
Am. J. Physiol.
272 (Regulatory Integrative Comp. Physiol. 41):
R1245-R1251,
1997
24.
Norgren, R.,
and
G. P. Smith.
A method for selective section of vagal afferent or efferent axons in the rat.
Am. J. Physiol.
267 (Regulatory Integrative Comp. Physiol. 36):
R1136-R1141,
1994
25.
Plata-Salaman, C. R.
Cytokines and feeding suppression: an integrative view from neurologic to molecular levels.
Nutrition
11:
674-677,
1995[Medline].
26.
Plata-Salaman, C. R.,
and
S. E. Ilyin.
Interleukin-1 (IL-1)-induced modulation of the hypothalamic IL-1 system, tumor necrosis factor-, and transforming growth factor-1 mRNAs in obese (fa/fa) and lean (Fa/Fa) Zucker rats: implications to IL-1 feedback systems and cytokine-cytokine interactions.
J. Neurosci. Res.
49:
541-550,
1997[Medline].
27.
Powley, T. L.,
E. A. Fox,
and
H. R. Berthoud.
Retrograde tracer technique for assessment of selective and total subdiaphragmatic vagotomies.
Am. J. Physiol.
253 (Regulatory Integrative Comp. Physiol. 22):
R361-R370,
1987
28.
Romanovsky, A. A.,
C. T. Simons,
M. Szekely,
and
V. A. Kulchitsky.
The vagus nerve in the thermoregulatory response to systemic inflammation.
Am. J. Physiol.
273 (Regulatory Integrative Comp. Physiol. 42):
R407-R413,
1997
29.
Schwartz, G. J.,
C. R. Plata-Salaman,
and
W. Langhans.
Subdiaphragmatic vagal deafferentation fails to block feeding suppressive effects of LPS and IL-1 in rats.
Am. J. Physiol.
273 (Regulatory Integrative Comp. Physiol. 42):
R1193-R1198,
1997
30.
Smith, G. P.,
C. Jerome,
and
R. Norgren.
Afferent axons in abdominal vagus mediate satiety effect of cholecystokinin in rats.
Am. J. Physiol.
249 (Regulatory Integrative Comp. Physiol. 18):
R638-R641,
1985
31.
Strack, A. M.,
W. B. Sawyer,
J. H. Hughes,
K. B. Platt,
and
A. D. Loewy.
A general pattern of CNS innervation of the sympathetic outflow demonstrated by transneuronal pseudorabies viral infections.
Brain Res.
491:
156-162,
1989[Medline].
32.
Wan, W.,
L. Wetmore,
C. M. Sorenson,
A. H. Greenberg,
and
D. M. Nance.
Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain.
Brain Res. Bull.
34:
7-14,
1994[Medline].
33.
Watkins, L. R.,
L. E. Goehler,
J. K. Relton,
N. Tartaglia,
L. Silbert,
D. Martin,
and
S. F. Maier.
Blockade of interleukin-1 induced hyperthermia by subdiaphragmatic vagotomy: evidence for vagal mediation of immune-brain communication.
Neurosci. Lett.
183:
27-31,
1995[Medline].
34.
Watkins, L. R.,
S. F. Maier,
and
L. E. Goehler.
Cytokine-to-brain communication: a review and analysis of alternative mechanisms.
Life Sci.
57:
1011-1026,
1995[Medline].
35.
Watkins, L. R.,
E. P. Wiertelak,
L. E. Goehler,
K. Mooney-Heiberger,
J. Martinez,
L. Furness,
K. P. Smith,
and
S. F. Maier.
Neurocircuitry of illness-induced hyperalgesia.
Brain Res.
639:
283-299,
1994[Medline].
This article has been cited by other articles:
|
|
 |
|
  L. Elander, L. Engstrom, M. Hallbeck, and A. Blomqvist IL-1beta and LPS induce anorexia by distinct mechanisms differentially dependent on microsomal prostaglandin E synthase-1 Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R258 - R267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Campisi,, M. K. Hansen,, K. A. O'Connor,, J. C. Biedenkapp,, L. R. Watkins,, S. F. Maier,, and M. Fleshner Circulating cytokines and endotoxin are not necessary for the activation of the sickness or corticosterone response produced by peripheral E. coli challenge J Appl Physiol, November 1, 2003; 95(5): 1873 - 1882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lugarini, B. J. Hrupka, G. J. Schwartz, C. R. Plata-Salaman, and W. Langhans A role for cyclooxygenase-2 in lipopolysaccharide-induced anorexia in rats Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2002; 283(4): R862 - R868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hosoi, Y. Okuma, A. Ono, and Y. Nomura Subdiaphragmatic vagotomy fails to inhibit intravenous leptin-induced IL-1beta expression in the hypothalamus Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R627 - R631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Emch, G. E. Hermann, and R. C. Rogers TNF-alpha -induced c-Fos generation in the nucleus of the solitary tract is blocked by NBQX and MK-801 Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2001; 281(5): R1394 - R1400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Hansen, K. A. O'Connor, L. E. Goehler, L. R. Watkins, and S. F. Maier The contribution of the vagus nerve in interleukin-1{beta}-induced fever is dependent on dose Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2001; 280(4): R929 - R934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. E. Hermann, G. S. Emch, C. A. Tovar, and R. C. Rogers c-Fos generation in the dorsal vagal complex after systemic endotoxin is not dependent on the vagus nerve Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2001; 280(1): R289 - R299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hosoi, Y. Okuma, and Y. Nomura Electrical stimulation of afferent vagus nerve induces IL-1beta expression in the brain and activates HPA axis Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2000; 279(1): R141 - R147. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
