| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Pediatrics and the 2 Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, Florida 33101
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Central administration of
interleukin-1
(IL-1) increases cerebral blood flow (CBF) and body
temperature, in part, through the production of prostaglandins. In
previous studies, the temporal relationship between these effects of
IL-1 have not been measured. In this study, we hypothesized that the
increase in CBF occurs before any change in brain or body temperature
and that the cerebrovascular and thermoregulatory effects of IL-1
would be attenuated by inhibiting the production of nitric oxide (NO).
Adult male rats received 100 ng intracerebroventricular (icv) injection
of IL-1, and cortical CBF (cCBF) was measured by laser-Doppler in
the contralateral cerebral cortex. A central injection of IL-1
caused a rapid increase in cCBF to 133 ± 12% of baseline within
15 min and to an average of 137 ± 12% for the remainder of the
3-h experiment. Brain and rectal temperature increased by 0.4 ± 0.2 and 0.5 ± 0.2°C, but not until 45 min after IL-1
administration. Pretreatment with N
-nitro-L-arginine methyl ester
(L-NAME; 5 mg/kg iv) completely prevented the changes in
cCBF and brain and rectal temperature induced by IL-1.
L-Arginine (150 mg/kg iv) partially reversed the effects of
L-NAME and resulted in increases in both cCBF and temperature. These findings suggest that the vasodilatory effects of
IL-1 in the cerebral vasculature are independent of temperature and
that NO plays a major role in both the cerebrovascular and thermoregulatory effects of centrally administered IL-1.
cytokines; cerebral blood flow; vasodilation; brain; fever; temperature; inflammation
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
INTERLEUKIN-1
(IL-1), a 17-kDa polypeptide possessing a wide spectrum of
inflammatory, metabolic, physiological, hematopoietic, and immunologic
activities, is produced by a variety of cells, including lymphocytes,
mononuclear phagocytes, and endothelial cells (13).
Intracerebroventricular (icv) injection of IL-1 causes pituitary
adrenal activation, hyperinsulinemia, slow-wave sleep, behavioral
changes, hypophagia, glial proliferation, neovascularization, peripheral neutrophilia, and fever (6, 10-13, 22, 31,
35). In a normal brain, low amounts of IL-1 have been
identified in microglia, astrocytes, and vascular endothelial cells,
predominantly in the hypothalamus, pituitary gland, hippocampus, and
cerebral cortex (47). IL-1 is produced in the brain in
response to central nervous system (CNS) and systemic infections
(19, 25) and to ischemic (32, 45, 48)
and traumatic brain injury (42), conditions that are
associated with both fever and alterations in cerebral blood flow (CBF)
(9, 16, 17).
Cerebral vasodilation after IL-1 injection has been shown to be
mediated, in part, by the prostaglandins, 6-keto-PGF1
, PGE2, and PGF2, through activation of
cyclooxygenase-1 (COX-1) and COX-2 (23, 36, 41). These
prostanoids are thought to cause early cerebral vasodilation by
accumulation of cyclic nucleotides (4) and, later, by
stimulation of the inducible form of nitric oxide (NO) synthase (iNOS)
in vascular smooth muscle and endothelial cells, thereby increasing the
production of NO (7, 14, 21).
In the CNS, the cells that have been found to be capable of NO
production include astrocytes, microglia, neurons, and endothelial cells. Neurons containing NOS have been identified in brain regions that participate in thermoregulation, such as the hypothalamic nuclei
and circumventricular organs, suggesting that NO may play a central
role in the regulation of temperature (3, 30, 39, 46).
Inhibition of NOS in experimental animal models of sepsis has
attenuated the height and duration of fever, providing indirect evidence that NO mediates the febrile response to IL-1 (15, 34, 37). However, the exact role of NO in thermoregulation has
not been clearly delineated (40).
Because the effect of temperature on the cerebrovascular response to
IL-1 has not been previously investigated, we designed the present
study to investigate the relationship between the cerebrovascular and
thermoregulatory responses to central injection of IL-1, and to
determine the role of NO in these responses. We hypothesized that
1) central injection of IL-1 increases cortical CBF
(cCBF) and brain and body temperature, 2) the
vasodilatory effects of IL-1 are independent of temperature, and
3) inhibition of NOS by L-NAME attenuates
the changes in CBF and temperature after central administration of
IL-1.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
This study was approved by the University of Miami Animal Care
and Use Committee. Young adult (2-3 mo) male Sprague-Dawley rats
were anesthetized with 5% isoflurane-70% nitrous oxide
(N2O), balance oxygen, and were endotracheally intubated
and ventilated with a rodent respirator (model 50095-1, Stoelting;
Wood Dale, IL) to achieve normal arterial blood gases. Anesthesia was
maintained with 1-2% isoflurane-70% N2O, balance
oxygen, and the rats were paralyzed with pancuronium (1 mg · kg
1 · h1 iv). The
femoral vessels were catheterized for measurement of mean arterial
pressure (MAP), blood sampling, and drug administration. A thermocouple
probe was inserted into the rectum to a distance of 8 cm for continuous
temperature monitoring, and then the animal was placed in a
stereoctatic frame to immobilize the cranium. The dorsal scalp was
reflected from 3 mm anterior to bregma to the posterior neck muscles. A
1-mm-diameter craniotomy was made 2 mm posterior and 3 mm lateral to
bregma on the right, through which a 30-gauge thermocouple probe was
inserted to a depth of 2 mm so that its tip would lie within the
cerebral cortex. A second craniotomy was made on the right 0.8 mm
posterior and 1.5 mm lateral to bregma for icv injection into the right
lateral ventricle. Icv injections (10 µl) were made by using a
micropipette at a depth of 4 mm into the right lateral ventricle over 2 min to prevent changes in intracranial pressure. On the left, a third
craniotomy, measuring 2 × 3 mm, was made 2 mm posterior and 3 mm
lateral to the bregma, exposing the intact dura. All of the
craniotomies were made under saline irrigation down to a thin layer of
bone, which was then excised with microforceps. To measure cCBF, a
0.8-mm-diameter laser-Doppler flow probe was positioned with a
micromanipulator adjacent to the dura over an area free of large
vessels in the lateral parietal cortex and connected to a tissue
perfusion monitor (model ALF-21D, Transonic Systems; Ithaca, NY).
The arterial catheter was connected to a Statham pressure transducer (model 13-4615-50, Gould; Cleveland, OH), which was calibrated before each experiment. Measurements of arterial blood pressure and cCBF were recorded continuously (model RS3600, Gould). Arterial blood gases and pH, and plasma glucose and lactate concentrations were measured hourly (model YSI 2300, Yellow Springs Instruments). Brain and rectal temperatures were recorded every 15 min.
After all of the surgical manipulations had been completed, isoflurane, but not N2O, was discontinued. The next 60 min were used to establish a stable baseline temperature and cCBF. During this time, rectal and brain temperatures were kept at 37.5 ± 0.3°C with the use of heating lamps. Once temperature stability was achieved, the position of the heating lamps was held constant for the remainder of the experiment.
The experiment was divided into two phases. The first phase was a
prospective, blinded study with two experimental groups. Group
I (n = 7) received 100 ng icv of heat-inactivated
IL-1 (75°C for 2 h) in artificial CSF. Group II
(n = 7) received 100 ng icv of recombinant rat IL-1
(Endogen; Woburn, MA) in artificial CSF. A single dose of IL-1 100 ng icv was chosen because in pilot studies this dose consistently
caused a significant and sustained increase in both CBF and rectal
temperature, as opposed to 25 or 50 ng IL-1. Groups
I and II were monitored for 180 min after administration of IL-1. In the second phase of the study,
Group III (n = 8) received
L-NAME 5 mg/kg iv 20 min before IL-1 (100 ng icv), and
the responses were monitored for 105 min. At minute 105, a
L-arginine 150 mg/kg iv bolus was given, followed by a continuous infusion 150 mg · kg1 · h1 iv for 75 min
to reverse the effects of L-NAME.
At the end of 3 h, the animals were euthanized with an overdose of
anesthetic and intravenous potassium chloride. Immunohistochemistry for
IL-1 was performed in four animals randomly selected from group II at 30, 45, and 60 min after icv injection of
IL-1, by using a polyclonal antibody to rat IL-1 (Endogen).
Transcardiac perfusion-fixation of the brain was performed with
ice-cold PBS (pH 7.4) for 1 min and ice-cold 4% paraformaldehyde (pH
7.4) for 5 min. The brains were quickly removed and placed in 4%
paraformaldehyde at 4°C for 24 h and then transferred to PBS
until sectioning. Coronal sections (50 µm) were obtained with the use
of a tissue sectioning device (Vibratome; St. Louis, MO) at four levels
from the anterior striatum to the anterior hippocampus.
Sections were then washed, quenched with H2O2,
and incubated with polyclonal rabbit anti-rat IL-1 (1:200) for
48 h at 4°C. After incubation, sections were washed and
incubated for 1 h with a biotinylated goat anti-rabbit IgG
antibody. They were washed again, incubated in diaminobenzidine
tetrahydrochloride for staining, mounted on glass slides, and examined
under light microscopy.
Measurements of brain and rectal temperature, MAP, and cortical CBF were averaged over 5 min for each time point. Data were analyzed by repeated-measures ANOVA with post hoc Bonferroni test. Values are expressed as means ± SE, with P < 0.05.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
There were no significant differences between groups for MAP,
cCBF, arterial blood gases, temperature, and plasma glucose and lactate
at baseline, and PaCO2 was tightly controlled between 35-40 mmHg throughout the experiment in all groups. Fifteen
minutes after icv injection of IL-1, cCBF increased to 133 ± 12% of baseline in group II (P < 0.05).
This increase in cCBF was sustained at an average of 137 ± 12%
of baseline for the remainder of the 3-h experiment (Fig.
1). Heat-inactivated IL-1 caused no
statistically significant changes in either cCBF or brain and rectal
temperature. After IL-1, brain and rectal temperature increased by
0.4 ± 0.2 and 0.5 ± 0.2°C, respectively, over baseline at
45 min after central injection of IL-1 and remained at an average of
0.7 ± 0.2 and 0.9 ± 0.2°C, respectively, above baseline
for the remainder of the experiment (Fig.
2). There was a strong correlation
between brain and rectal temperature (R2 = 0.91, P < 0.01) in all experimental groups, with an
average rectal-brain difference of 0.3°C. The observed increase in
cCBF preceded the observed increase in brain temperature by ~30 min (Fig. 3).
|
|
|
In group III, L-NAME increased MAP from 128 ± 1 to 156 ± 3 mmHg within 15 min (Fig.
4), lowered rectal temperature from
37.7 ± 0.08 to 37.5 ± 0.09 (P < 0.01), and
did not alter brain temperature. Before IL-1, L-NAME
also reduced cCBF by 20 ± 4% (P < 0.01). In the
presence of L-NAME, IL-1 had no effect on either cCBF or
brain and rectal temperature (Figs. 5 and
6). When
L-arginine was given 105 min after central injection of
IL-1, MAP, cCBF, and brain and rectal temperature returned to
baseline (Figs. 5 and 6).
|
|
|
Immunohistochemistry revealed IL-1-positive cells in the superficial
cerebral cortex and the periventricular surfaces (Fig. 7). This showed that after the icv
injection, IL-1 was widely distributed over the brain cortex and
periventricular region, with only superficial penetration at the time
points studied. Specificity of the primary antibody was confirmed when
no immunoreaction product was present after preadsorption with
recombinant rat IL-1 at a molar ratio of 1:2.5.
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
These data show that the early increase in cCBF after central
injection of IL-1 is independent of temperature and that NO plays a
major role in both the cerebrovascular and thermoregulatory effects of
IL-1. This study is unique in that we measured these two important
effects of IL-1 simultaneously in the same animals. Our findings
support the idea that the pathways for the production of NO and
prostaglandins in response to IL-1 are in series (4, 28, 36,
41) rather than in parallel (34).
The cerebrovascular effects of IL-1 have been studied in a variety
of experimental paradigms. Direct application or superfusion of IL-1
onto cerebral arteries has demonstrated rapid increases in vessel
diameter associated with elevations in CSF concentration of eicosanoids
and cGMP (27, 41, 43). With the use of the closed cranial
window technique on newborn piglets, Shibata et al. (41)
found that IL-1 increased pial arteriolar diameter by 18.6% within
10 min, accompanied by increases in CSF concentrations of prostanoids,
cAMP and cGMP. Osuka et al. (28) measured a 28% increase
in basilar artery diameter 2 h after application of IL-1. In
both of these studies, the vasodilatory effects of IL-1 were
prevented by pretreatment with COX inhibitors, suggesting a role for
both prostanoids and NO in the vasodilation induced by IL-1.
Armstead (4) demonstrated that the vasodilatory effects of
the prostaglandins PGI2 and PGE2 are partially
dependent on NO production, because the NOS inhibitor
L-NAME attenuated prostaglandin-induced vasodilation. Other
investigators have shown that PGD2 plays an important role
in the rat's response to IL-1 (44) and in preventing the upregulation of iNOS in vascular smooth muscle cells
(17). In the present study, we measured a 40% increase in
cCBF 15 min after central administration of IL-1, which was
completely prevented by L-NAME. Such a rapid increase in
cCBF after IL-1 probably reflects activation of cNOS (5, 18,
26) rather than iNOS, because several studies (7, 21,
47) have shown that upregulation of the latter isoform of NOS
does not occur until at least 6 h after administration of IL-1.
The thermoregulatory effects of IL-1 have been well studied;
however, the role of NO in this response has not been clearly delineated [for review, see Schmid et al. (40)]. As is
the case for IL-1-induced vasodilation, PGE2 has been
thought to be the primary mediator of the febrile response to IL-1
(12, 13, 22, 35). More recently, NO has been found to play
an important role in thermoregulation, although conflicting studies
have shown both pyretic and antipyretic effects of NO. Almeida et al.
(1) found that centrally injected L-NAME
increased body temperature and enhanced the febrile response to LPS. In
contrast, systemic administration of either L-NAME or the
neuronal NOS inhibitor 7-nitroindazole lowers body temperature and
inhibits the rise in temperature after LPS infusion (8, 34,
37). Although the systemic vasoconstrictive effects of
L-NAME should decrease heat loss through the skin and thus
elevate core temperature, we found that L-NAME decreased
rectal temperature and prevented the febrile response to central
administration of IL-1. Roth et al. (33) reported
similar results in rabbits that were given both IL-1 and
L-NAME intraperitoneally, the latter at 10× the dose used
in our study. In that study, no attempt was made to reverse the effects
of L-NAME. When L-arginine was given 105 min after L-NAME in our study, both cCBF and temperature
increased significantly to pre-L-NAME values but did not
reach the levels seen in rats that received IL-1 alone. The
incomplete reversal of the effects of L-NAME could have
been due to an inadequate dose of L-arginine, although in
pilot studies in rats in our lab and in infant piglets, complete
reversal of the hemodynamic effects of L-NAME were achieved
with L-arginine at 30× the dose of L-NAME (38). A more likely explanation is that insufficient
IL-1 was present in CSF at the time of reversal with
L-arginine, due to rapid clearance or metabolism of
centrally administered IL-1 (12).
In the absence of L-NAME, IL-1 increased cCBF and,
later, brain and body temperature. The delayed elevation in brain
temperature did not further increase cCBF over the level induced
initially by IL-1. The apparent lack of additive effects of IL-1
and fever on cCBF could be explained by the following possibilities:
1) that IL-1 and fever increase cCBF by the same
mechanism, e.g., through the production of NO, 2) that the
increase in brain temperature was too small to cause a change in cCBF,
and 3) that the laser-Doppler method of measuring CBF was
not sensitive enough to detect a small change in cCBF, which may have
occurred when brain temperature increased after IL-1 was given.
Alternatively, the vasodilatory effects of IL-1 may have been
receding at the same time that the same effects of fever were
beginning, yielding no change in cCBF.
Another interesting issue relates to the separate roles of NO and
prostaglandins in the effects of IL-1 on CBF and temperature. Assuming that both compounds are involved in these effects of IL-1,
the following questions arise concerning their synthetic pathways:
1) are they in series or in parallel;
2) are they convergent or divergent; 3)
which is produced first and in greater amounts; and 4)
are there cell-specific differences in the effect of IL-1 on these
pathways? These questions require further investigation.
In conclusion, we found that the increases in both cCBF and temperature
in response to IL-1 were completely prevented by pretreatment with
the nonselective NOS inhibitor, L-NAME, suggesting that NO
plays an important role in these responses to IL-1. Cortical CBF
increased before hyperthermia occurred, indicating that the early
cerebrovascular effects of IL-1 are independent of temperature. Our
findings underscore the important role of NO in brain disorders such as
meningitis (19, 25), stroke (20, 24, 32, 45, 48), and traumatic brain injury (42) in which
inflammatory cytokines may augment the primary injury as well as cause
disturbances in thermoregulation leading to fever. Whereas the
cerebrovascular effects of NO are clearly vasodilatory in the presence
of IL-1, it appears that the thermoregulatory effects of NO depends
upon the dose and species studied, the route of administration and the
site and cell types in the brain involved in its production and action
(40).
| |
ACKNOWLEDGEMENTS |
|---|
This study was supported by National Institute of Neurological Disorders and Stroke Grants KO8 NS01890-03 (to J. W. Kuluz) and PO1 NS30291-06A1 (to W. D. Dietrich).
| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: J. W. Kuluz, Dept. of Pediatrics (R-131), PO Box 016960, Miami, FL 33101 (E-mail: jkuluz{at}med.miami.edu).
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. Section 1734 solely to indicate this fact.
Received 17 July 2000; accepted in final form 14 November 2000.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Almeida, MC,
Trevisan FN,
Barrios RCH,
Carnio EC,
and
Branco LGS
Tolerance to lipopolysaccharide is related to the nitric oxide pathway.
Neuroreport
10:
3061-3065,
1999[Web of Science][Medline].
2.
Arevalo, R,
Sanchez F,
Alonso JR,
Carretero J,
Vasquez R,
and
Aiyon J.
NADPH-diaphorase activity in the hypothalamic magnocellular neurosecretary nuclei.
Brain Res Bull
28:
599-603,
1992[Web of Science][Medline].
3.
Ariano, MA.
Distribution of components of the guanosine 3', 5'-phosphate system in rat caudate-putamen.
Neuroscience
10:
707,
1983[Web of Science][Medline].
4.
Armstead, WM.
Role of nitric oxide and cAMP in prostanoid-induced pial arteriolar vasodilation.
Am J Physiol Heart Circ Physiol
268:
H1436-H1440,
1995
5.
Beasley, D,
Schwartz JH,
and
Brenner BM.
Interleukin-1 induced prolonged L-arginine-dependent cyclic guanosine monophosphate and nitrite production in rat vascular smooth muscle cells.
J Clin Invest
87:
602-608,
1991.
6.
Berkenbosch, F,
Van Oers J,
del Rey A,
Tilders F,
and
Basedovsky H.
Corticotrophin-releasing factor-producing neurons in the rat activated by interleukin-1.
Science
238:
524-526,
1987
7.
Bonmann, E,
Suschek C,
Spranger M,
and
Kolb-Bachofen V.
The dominant role of exogenous or endogenous interleukin-1 beta on expression and activity of inducible nitric oxide synthase in rat microvascular brain endothelial cells.
Neurosci Lett
230:
109-112,
1997[Web of Science][Medline].
8.
Callahan, BT,
and
Ricaurte GA.
Effect of 7-nitroindazole on body temperature and methamphetamine-induced dopamine toxicity.
Neuroreport
9:
2691-2695,
1998[Web of Science][Medline].
9.
Childers, MK,
Rupright J,
and
Smith DW.
Post-traumatic hyperthermia in acute brain injury rehabilitation.
Brain Inj
8:
335-343,
1994[Web of Science][Medline].
10.
Coceaui, F.
Prostaglandin and fever.
In: Basic Mechanisms and Management, Facts and Controversies, edited by Mackowiak P.. New York: Raven, 1991, p. 59-70.
11.
Cornell, RP,
and
Schwartz DB.
Central administration of interleukin-1 elicits hyperinsulinemia in rats.
Am J Physiol Regulatory Integrative Comp Physiol
256:
R772-R777,
1989
12.
Dinarello, CA.
Interleukin-1.
In: The Cytokine Handbook. New York: Academic, 1991, p. 47-75.
13.
Dinarello, CA,
Cannon JC,
and
Wolff SM.
New concepts on the pathogenesis of fever.
Rev Infect Dis
10:
168-189,
1988[Web of Science][Medline].
14.
Eckhard, B,
Suschek C,
Springuer M,
and
Kolb-Bachofen V.
The dominant role of exogenous or endogenous interleukin-1 on expression and activity of inducible nitric oxide synthase in rat microvascular brain endothelial cells.
Neurosci Lett
230:
109-112,
1997.
15.
Evans, T,
Carpenter A,
Silva A,
and
Cohen J.
Inhibition of nitric oxide synthase in experimental gram-negative sepsis.
J Infect Dis
169:
343-349,
1994[Web of Science][Medline].
16.
Georgilis, K,
Plomaritoglou A,
Dafni U,
Bassiakos Y,
and
Vemmos K.
Aetiology of fever in patients with acute stroke.
J Intern Med
246:
203-209,
1999[Web of Science][Medline].
17.
Grau, AJ,
Buggle F,
Schnitzler P,
Spiel M,
Lichy C,
and
Hacke W.
Fever and infection early after ischemic stroke.
J Neurol Sci
171:
115-120,
1999[Web of Science][Medline].
18.
Ignarro, LJ,
Buga GM,
Wood KS,
Byrus RE,
and
Chaudhuri G.
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
Proc Natl Acad Sci USA
84:
9265-9269,
1987
19.
Jain, M,
Aneja S,
Mehta G,
Ray GN,
Batra S,
and
Randhava VS.
CSF interleukin-1s, tumor necrosis factor-
and free radicals production in relation to clinical outcome in acute bacterial meningitis.
Indian Pediatr
37:
608-614,
2000[Medline].
20.
Kadoya, C,
Domino EF,
Yang GY,
Stern JD,
and
Betz AL.
Preischemic but not postischemic zinc protoporphyrin treatment reduces infarct size and edema accumulation after temporary focal cerebral ischemia in rats.
Stroke
26:
1035-1038,
1995
21.
Kanno, K,
Hirata Y,
Imai T,
Iwashina M,
and
Mavuma F.
Regulation of inducible nitric oxide synthase gene by interleukin-1 in rat vascular endothelial cells.
Am J Physiol Heart Circ Physiol
267:
H2318-H2324,
1994
22.
Kluger, MJ.
Role of pyrogens and cryogens.
Physiol Rev
71:
93-127,
1991[Abstract].
23.
Lin, JH,
and
Lin MT.
Nitric oxide synthase-cyclooxygenase pathway in organum vasculosum laminae terminalis: possible role in pyrogenic fever in rabbits.
Br J Pharmacol
118:
179-182,
1996[Web of Science][Medline].
24.
Liu, T,
McDonnell PC,
Young PR,
White RF,
Sireu AL,
Hallenback JM,
Barone FC,
and
Feurestein GZ.
Interleukin-1 mRNA expression in ischemic rat cortex.
Stroke
24:
1746-1751,
1993
25.
Lopez-Cortes, LF,
Marquez-Arbizu R,
Jimenez-Jimenez LM,
Jimenez-Mejias E,
Caballero-Granado FJ,
Rey-Romero C,
Polaina M,
and
Pachon J.
Cerebrospinal fluid tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interleukin-8 as diagnostic markers of cerebrospinal fluid infection in neurosurgical patients.
Crit Care Med
28:
215-219,
2000[Web of Science][Medline].
26.
Monda, M,
Amaro S,
Sullo A,
and
De Luca B.
Nitric oxide reduces body temperature and sympathetic input to brown adipose tissue during PGE1 hyperthermia.
Brain Res Bull
3:
489-493,
1995.
27.
Nagoshi, H,
Euhara Y,
Kanai F,
Maeda S,
Ogura T,
At. Goto Toyo-oko T,
Esumi H,
Shimizu T,
and
Omata M.
Prostaglandin D2 inhibits inducible nitric oxide synthase expression in rat vascular smooth muscle cells.
Circ Res
82:
204-209,
1998
28.
Osuka, K,
Susuki Y,
Watanabe Y,
Dogan A,
Takayasu M,
Shibua M,
and
Yoshida J.
Vasodilator effects on canine basilar artery induced by intracistarnal interleukin-1.
J Cereb Blood Flow Metab
17:
1337-1345,
1997[Web of Science][Medline].
29.
Palmer, RMJ,
Rees DD,
Ashton DS,
and
Moncada S.
L-Arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation.
Biochem Biophys Res Commun
153:
1251-1256,
1988[Web of Science][Medline].
30.
Pow, DA.
NADPH-diaphorase (nitric oxide synthase) staining in the rat supraoptic nucleus is activity-dependent; possible functional implications.
J Neuroendocrinol
4:
377-380,
1992.
31.
Reimers, JI,
Bjerre U,
Mandrup-Poulsen T,
and
Nerup J.
Interleukin-1 induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide syntheses.
Cytokine
6:
512-520,
1994[Web of Science][Medline].
32.
Relton, JK,
and
Rothwell NJ.
Interleukin-1 receptor antagonist inhibits ischemic and excitotoxic neuronal damage in the rat.
Brain Res Bull
29:
243-246,
1992[Web of Science][Medline].
33.
Roth, J,
Storr B,
Voigt K,
and
Zeisberger E.
Inhibition of nitric oxide synthase results in a suppression of interleukin-1 induced fever in rats.
Life Sci
3:
PL345-PL350,
1998.
34.
Roth, J,
Storr B,
Voigt K,
and
Zeisberger E.
Inhibition of nitric oxide synthase attenuates lipopolysaccharide-induced fever without reduction of circulating cytokines in guinea-pigs.
Pflügers Arch
436:
858-862,
1998[Web of Science][Medline].
35.
Rothwell, NJ.
Eicosanoids, thermogenesis and thermoregulation.
Prostaglandins Leukot Essent Fatty Acids
46:
1-7,
1992[Web of Science][Medline].
36.
Salvemini, D,
Misko TP,
Masferrer JL,
Seibert K,
Currie MG,
and
Needleman P.
Nitric oxide activates cyclooxygenase enzymes.
Proc Natl Acad Sci USA
90:
7240-7244,
1993
37.
Scammell, TE,
Elmquist JK,
and
Saper CB.
Inhibition of nitric oxide synthase produces hypothermia and depresses lipopolysaccharide fever.
Am J Physiol Regulatory Integrative Comp Physiol
271:
R333-R338,
1996
38.
Schleien, CL,
Kuluz JW,
and
Gelman B.
Hemodynamic effects of nitric oxide synthase inhibition before and after cardiac arrest in infant piglets.
Am J Physiol Heart Circ Physiol
274:
H1378-H1385,
1998
39.
Schmid, HA,
Jansky L,
and
Pierau FK.
Temperature sensitivity of neurons in slices of the rat PO/AH area: effect of bombesin and substance P.
Am J Physiol Regulatory Integrative Comp Physiol
264:
R449-R455,
1993
40.
Schmid, HA,
Riedel W,
and
Simon E.
Role of nitric oxide in temperature regulation.
Prog Brain Res
115:
87-110,
1998[Web of Science][Medline].
41.
Shibata, M,
Lefler CW,
and
Busija DW.
Recombinant human interleukin-1 dilates pial arterioles and increases cerebrospinal fluid prostanoids in piglets.
Am J Physiol Heart Circ Physiol
259:
H1486-H1499,
1990
42.
Stahel, PF,
Shohami E,
Younis FM,
Kariya K,
Otto VI,
Lenzlinger PM,
Grosjean MB,
Eugster HP,
Trentz O,
Kossmann T,
and
Morganti-Kossmann MC.
Experimental closed head injury: analysis of neurological outcome, blood-brain barrier dysfunction, intracranial neutrophil infiltration, and neuronal cell death in mice deficient in genes for pro-inflammatory cytokines.
J Cereb Blood Flow Metab
20:
369-380,
2000[Web of Science][Medline].
43.
Takizawa, S,
Ozaki H,
and
Karaki H.
Interleukin-1-induced, nitric oxide-dependent and -independent inhibition of vascular smooth muscle contraction.
Eur J Pharmacol
330:
143-150,
1997[Web of Science][Medline].
44.
Terao, A,
Matsumura H,
and
Saito M.
Interleukin-1 induces slow-wave sleep at the prostaglandin D2-sensitive sleep-promoting zone in the rat brain.
J Neurosci
18:
6599-6607,
1998
45.
Touzani, O,
Boutin H,
Chuquet J,
and
Rothwell N.
Potential mechanisms of interleukin-1 involvement in cerebral ischaemia.
J Neuroimmunol
100:
203-215,
1999[Web of Science][Medline].
46.
Vincent, SR,
and
Kimura H.
Histochemical mapping of nitric oxide synthase in the rat brain.
Neuroscience
46:
755-784,
1992[Web of Science][Medline].
47.
Wong, ML,
Bongiorno PB,
Al-Shekhlee A,
Esposito A,
Khatri P,
and
Licinio J.
IL-1, IL-1 receptor type I and iNOS gene expression in rat brain vasculature and perivascular areas.
Neuroreport
7:
2445-2448,
1996[Web of Science][Medline].
48.
Yamasaki, Y,
Matsuura N,
Shozuhara H,
Ouodera H,
Itoyama Y,
and
Kogure K.
Interleukin-1 as a photogenic mediator of ischemic brain damage in rats.
Stroke
26:
676-681,
1995
This article has been cited by other articles:
|
|
 |
|
  A. C. Ribeiro and L. Kapas Day- and nighttime injection of a nitric oxide synthase inhibitor elicits opposite sleep responses in rats Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R521 - R531. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Kenney, F. Blecha, R. J. Fels, and D. A. Morgan Altered frequency responses of sympathetic nerve discharge bursts after IL-1beta and mild hypothermia J Appl Physiol, July 1, 2002; 93(1): 280 - 288. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
) and brain
(
) temperature increased after IL-1
15), IL-1
