Synergistic interaction of corticotropin releasing factor and arginine vasopressin on adrenocorticotropin and cortisol secretion in Macaca fuscata

Plasma immunoreactive CRF measured by radioimmunoassay decreased rapidly after intravenous injection of synthetic ovine corticotropin releasing factor (CRF) and showed a bi-exponential decay curve in five macaca fuscatas. Half lives of plasma immunoreactive CRF were 5.8 +/- 1.4 (Mean +/- SEM) min for the fast component and 38.3 +/- 2.4 min for the slow component. A bolus injection of 5 micrograms/kg CRF significantly increased the plasma cortisol level. CRF at 5 micrograms/kg induced a delayed response of ACTH and cortisol. Arginine vasopressin (AVP) at 0.5 micrograms/kg induced a slight increase in plasma ACTH and cortisol, but AVP at 0.1 micrograms/kg evoked no significant increase. When 0.5 micrograms/kg CRF and 0.1 micrograms/kg AVP were administered simultaneously, significant ACTH and cortisol responses occurred. The results indicate that CRF and AVP act synergistically to stimulate ACTH secretion in vivo.     

Prostaglandin mediates endotoxaemia-induced hypophagia by activation of pro-opiomelanocortin and corticotrophin-releasing factor neurons in rats

Corticotrophin-releasing factor (CRF) and α-melanocyte-stimulating hormone (α-MSH), both of which are synthesized by hypothalamic neurons, play an essential role in the control of energy homeostasis. Neuroendocrine and behavioural responses induced by lipopolyssacharide (LPS) have been shown to involve prostaglandin-mediated pathways. This study investigated the effects of prostaglandin on CRF and α-MSH neuronal activities in LPS-induced anorexia. Male Wistar rats were pretreated with indomethacin (10 mg kg⁻¹; i.p .) or vehicle; 15 min later they received LPS (500 μg kg⁻¹; i.p .) or saline injection. Food intake, hormone responses and Fos–CRF and Fos–α-MSH immunoreactivity in the paraventricular and arcuate nuclei, respectively, were evaluated. In comparison with saline treatment, LPS administration induced lower food intake and increased plasma ACTH and corticosterone levels, as well as an increase in Fos–CRF and Fos–α-MSH double-labelled neurons in vehicle-pretreated rats. In contrast, indomethacin treatment partly reversed the hypophagic effect, blunted the hormonal increase and blocked the Fos–CRF and Fos–α-MSH hypothalamic double labelling increase in response to the LPS stimulus. These data demonstrate that the activation of pro-opiomelanocortin and CRF hypothalamic neurons following LPS administration is at least partly mediated by the prostaglandin pathway and is likely to be involved in the modulation of feeding behaviour during endotoxaemia.     

Evidence that intravenous administration of interleukin-1 stimulates corticotropin releasing hormone secretion in the median eminence of freely moving rats: estimation by push-pull perfusion.

Utilizing push-pull perfusion, we examined secretory profiles of corticotropin releasing hormone (CRH) in the median eminence (ME) and of plasma adrenocorticotropin (ACTH) in freely moving male rats after intravenous bolus injection of recombinant human interleukin (IL)-1 alpha (1.0 microgram) and 1 beta (1.0 microgram). The ME was perfused with artificial cerebrospinal fluid between 11.00 and 14.00 h, and perfusates and blood samples were collected every 20 min. Administrations at 12.00 h of IL-1 alpha and 1 beta, but not vehicle only, resulted in significant increases in both the plasma ACTH and ME-CRH. The rise in ME-CRH clearly preceded the enhanced ACTH secretion. These in vivo data strongly suggest that IL-1 stimulates ACTH secretion, at least in part, by triggering hypothalamic CRH release. This is the first to characterize the temporal profile of CRH secretion in the ME after intravenous administration of IL-1 to freely moving rats.     

A novel permissive role for glucocorticoids in induction of febrile and behavioral signs of experimental herpes simplex virus encephalitis.

Herpes simplex virus type 1 (HSV-1) encephalitis may present with fever and behavioral changes, to the extent of a psychotic state and psychomotor agitation. We developed a clinically relevant experimental model of HSV-1 encephalitis and investigated host brain responses associated with its clinical signs and whether these responses depend on the presence of circulating glucocorticoids. Intracerebral inoculation of HSV-1 in rats induced fever, motor hyperactivity and aggressive behavior. In adrenalectomized rats HSV-1 failed to induce these signs, although mortality rate was identical to sham-operated rats. Hypophysectomy or blocking glucocorticoid receptors also prevented HSV-1-induced fever. Dexamethasone replacement therapy to adrenalectomized rats restored the HSV-1-induced fever and behavioral abnormalities. HSV-1 inoculation produced hyperproduction of prostaglandin E(2) by brain slices. This effect was abolished in adrenalectomized rats and was restored by dexamethasone treatment. In intact rats HSV-1 induced brain interleukin-1beta (IL-1beta) gene expression. Adrenalectomy alone caused brain IL-1beta expression, which did not increase after HSV-1 infection. Similarly, HSV-1 induced IL-1beta expression in astrocyte cultures. Removal of cortisol from the culture medium caused basal IL-1beta mRNA expression which was not increased by infection.In conclusion, fever, motor hyperactivity and aggressive behavior during experimental HSV-1 encephalitis are dependent on brain responses, including prostaglandin E(2) and IL-1beta synthesis. Circulating glucocorticoids play an essential permissive role in the induction of these host brain responses.     

Participation of capsaicin-sensitive afferent neurons in gastric motor inhibition caused by laparotomy and intraperitoneal acid.

Stimulation of somatic or visceral nociceptors causes changes in gastrointestinal motor activity and blood pressure. The present study examined the possible participation of capsaicin-sensitive afferent and noradrenergic efferent neurons in the blood pressure and gastric motor responses to laparotomy and intraperitoneal injection of capsaicin or hydrochloric acid in the rat. Gastric motor activity was measured by recording the intragastric pressure of phenobarbital-anaesthetized rats via an oesophageal catheter. Laparotomy as well as intraperitoneal injection of capsaicin (33 and 330 microM) or hydrochloric acid (30 mM) caused a transient reduction of gastric motor activity stimulated by intravenous infusion of bombesin (200 pmol/min) and a brief fall of blood pressure (depressor effect). The depressor effect of laparotomy was followed by prolonged hypertension. Defunctionalization of capsaicin-sensitive afferent neurons by systemic pretreatment of rats with capsaicin (0.4 mmol/kg) prevented the depressor effect and gastric motor inhibition elicited by laparotomy, intraperitoneal capsaicin (33 microM) or intraperitoneal hydrochloric acid (30 mM). However, the effects of 330 microM capsaicin on blood pressure and gastric motility were only partially reduced by capsaicin pretreatment. Blockade of noradrenergic sympathetic neurons by pretreating rats with guanethidine (0.225 mmol/kg) prevented the gastric motor inhibition and depressor effects of laparotomy and intraperitoneal injection of hydrochloric acid (30 mM). The inhibition of gastric motility caused by capsaicin (33 and 330 microM) was only partially reduced by guanethidine pretreatment. The secondary hypertension following the depressor effect of intraperitoneal capsaicin or hydrochloric acid was enhanced in guanethidine-pretreated rats whereas the prolonged hypertension induced by laparotomy was left unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of prostaglandin E2 on the body temperature of restrained rats

We examined the effects of intravenous (IV) or intracerebro-ventricular (ICV) injection of prostaglandin E2 (PGE2) on the rectal temperature of restrained rats. The IV injection of PGE2 (0.5 mg/kg) caused hypothermia in rats with high initial rectal temperatures, but caused an elevation in rectal temperature in those animals whose starting temperatures were low. In contrast, the ICV injection of PGE2 induced fever, regardless of the rectal temperature at the time of injection. We also examined whether temperature changes due to the IV injection of endotoxin (lipopolysaccharide, LPS, 10 micrograms/kg) or interleukin-1 beta(IL-1 beta, 0.2 micrograms/kg) were dependent upon the rats' initial rectal temperatures. Rats with low rectal temperatures developed fevers in response to LPS, while animals with high starting temperatures showed hypothermia. In contrast, the IV injection of IL-1 beta produced fever regardless of initial rectal temperature. These data suggest that PGE2 acts centrally to cause fever and peripherally to cause hypothermia, and that following the injection of LPS, these opposing actions of PGE2 may act together to determine the thermoregulatory response.     

Hyponatremia and inflammation]

We experienced four cases with hyponatremia due to SIADH, which seems to be related to inflammation. The plasma Na concentration decreased when the patients had fever and increased plasma CRP level. In such conditions, plasma vasopressin concentration (PAVP) and the plasma interleukin-6 (IL-6) concentration were increased. There was significant correlation between them. The animal experiments were carried out to investigate the role of interleukin in the development of SIADH. Intravenous administrations of IL-1 beta increased AVP, atrial natriuretic hormone (ANH) and ACTH. The changes in AVP and ACTH were abolished by the pretreatment with an intravenous administration of indomatacin. Moreover, the intracerebroventricular administration (ICV) of IL-1 beta also increased AVP, atrial natriuretic hormone (ANH) and ACTH. The pretreatment of indomatacin attenuated the changes in AVP and ACTH. The intravenous administration of IL-1 beta increased the urinary sodium excretion. The pretreatement of HS142-1, an ANH antagonist, abolished the increase in urinary sodium excretion induced by IL-1 beta. These results suggested that the interleukin play an important role in the development of SIADH associated with inflammation.     

Role of Kupffer cells in developing streptococcal cell wall granulomas. Streptococcal cell wall induction of inflammatory cytokines and mediators.

Hepatic granulomas are induced by intraperitoneal injection of streptococcal cell walls (SCW) into Lewis rats. Kupffer cells rapidly clear SCW from the blood, and the authors examined Kupffer cells further for a role in SCW-hepatic inflammation. Isolated Kupffer cells cultured with SCW secreted high levels of tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), transforming growth factor beta (TGF beta), and prostaglandin E2 (PGE2). SCW transiently induced increased steady-state levels of IL-1 beta and TNF alpha mRNA; in contrast, constitutive expression of TGF beta 1 mRNA in Kupffer cells was not affected by SCW. Low concentrations of SCW induced the accumulation of intracellular IL-1 and TGF beta bioactivity, with intracellular IL-1 bioactivity remaining high through at least 72 hours of culture. Kupffer cells isolated 1, 7, and 21 days after SCW injection did not express IL-1 beta or TNF alpha mRNA greater than control levels and exhibited marked hyporesponsiveness to secondary in vitro stimulation with SCW or LPS. SCW transiently induces Kupffer cells to secrete a variety of soluble mediators that contribute to hepatic inflammation by inducing leukocyte recruitment and activation and fibroproliferation. The transient nature of the Kupffer cell response and the hyporesponsiveness to secondary stimulation may be a mechanism by which the hepatic inflammation is negatively regulated.     

Sympathetic influence on capsaicin-evoked enhancement of dorsal root reflexes in rats

A series of experiments by our group suggest that the initiation and development of neurogenic inflammation in rats are mainly mediated by dorsal root reflexes (DRRs), which are conducted centrifugally from the spinal dorsal horn in primary afferent nocieptors. In this study, DRRs were recorded in anesthetized rats from single afferent fibers in the proximal ends of cut dorsal root filaments at the L4-L6 level and tested for responses to intradermal injection of capsaicin. Sympathectomy combined with pharmacological manipulations were employed to determine if the capsaicin-evoked enhancement of DRRs was subject to sympathetic modulation. DRRs could be recorded from both myelinated (Abeta and Adelta) and unmyelinated (C) afferent fibers. After capsaicin was injected intradermally into the plantar foot, a significant enhancement of DRRs was seen in C- and Adelta-fibers but not in Abeta-fibers. This enhancement of DRRs evoked by capsaicin injection was almost completely prevented by sympathectomy. However, if peripheral alpha1-adrenoceptors were activated by intra-arterial injection of phenylephrine, the enhancement of DRRs evoked by capsaicin could be restored, whereas no such restoration was seen following pretreatment with an alpha2-adrenoceptor agonist, UK14,304. Under sympathetically intact conditions, the enhanced DRRs following capsaicin injection could be blocked by administration of terazosin, an alpha1-adrenoceptor antagonist, but not by administration of yohimbine, an alpha2-adrenoceptor antagonist. These results provide further evidence that the DRR-mediated neurogenic inflammation depends in part on intact sympathetic efferents acting on peripheral alpha1-adrenoceptors, which augment the sensitization of primary afferent nociceptors induced by capsaicin injection, helping trigger DRRs that produce vasodilation.     

Interleukin-1 beta production in the rabbit brain during endotoxin-induced fever.

Interleukin-1 beta (IL-1 beta) production in the brain and the spleen was investigated in rabbits made febrile by intravenous (I.V.) injection of endotoxin, or human recombinant IL-1 beta (hIL-1 beta). The endotoxin used in the present study was the lipopolysaccharide (LPS) of Salmonella typhosa endotoxin. Monophasic fever was induced by I.V. injection of a low dose of LPS (0.02 micrograms kg-1) and biphasic fever by I.V. injection of a large dose of LPS (4 micrograms kg-1), a sublethal dose of LPS (40 micrograms kg-1) or hIL-1 beta (2 micrograms kg-1). In situ hybridization and immunohistochemical studies revealed that, although no IL-1 beta production was observed in the brain at 1 and 3 h after injection of a low dose of LPS (0.02 micrograms kg-1) or of hIL-1 beta (2 micrograms kg-1), IL-1 beta production was demonstrated in organum vasculosum laminae terminalis (OVLT) and some cells around the blood vessels in the parenchyma 1 h after 4 micrograms kg-1 LPS. IL-1 beta production was detected throughout the brain after 40 micrograms kg-1 LPS. Pretreatment with indomethacin, an inhibitor of prostaglandin synthesis, did not affect IL-1 beta production in the brain induced by 4 micrograms kg-1 LPS. The cell type which produces IL-1 beta in the OVLT following LPS injection was confirmed to be a macrophage by electron microscopy. The cells producing IL-1 beta in the parenchyma were determined to be microglial cells. In the spleen, each dose of LPS induced a significant increase in IL-1 beta production in polymorphonuclear cells and macrophages in the red pulp 1 h after injection. However, 2 micrograms kg-1 hIL-1 beta did not induce IL-1 beta production in the spleen. The present results show clearly that systemic administration of LPS induces IL-1 beta production in the OVLT which may be responsible for induction of the second phase of biphasic fever. The production of IL-1 beta in the OVLT was not attributable to the action of peripherally synthesized IL-1 beta or prostaglandins.     

In vivo vitamin E administration attenuates interleukin-6 and interleukin-1beta responses to an acute inflammatory insult in mouse skeletal and cardiac muscle

Antioxidants are associated with reduced pro-inflammatory cytokine expression in immune cells and isolated tissues; however, no studies have examined whether short-term vitamin E administration is associated with reduced lipopolysaccharide (LPS)-induced cytokine expression in mouse skeletal and cardiac muscle, in vivo. These experiments tested the hypothesis that vitamin E administration attenuates nuclear factor kappaB (NF-kappaB), IL-6, IL-1beta and tumour necrosis factor alpha (TNFalpha) responses in skeletal and cardiac muscle to an inflammatory challenge induced by systemic LPS. We compared IL-6, IL-1beta and TNFalpha mRNA and protein, activated NF-kappaB and total oxidized proteins in skeletal and cardiac muscle 4 or 24 h after saline or LPS injection in mice receiving vitamin E or placebo for 3 days prior to the insult. Skeletal and cardiac IL-6 mRNA and protein were significantly elevated by LPS in both groups, but responses were significantly lower in vitamin E- compared with placebo-treated mice. In skeletal and cardiac muscle, LPS increased IL-1beta mRNA and protein in placebo- but not vitamin E-treated mice. Lipopolysaccharide-induced levels of cardiac IL-1beta mRNA and protein and skeletal IL-1beta mRNA were lower with vitamin E than placebo. Lipopolysaccharide-induced NF-kappaB activation and increases in total oxidized proteins were attenuated with vitamin E compared with placebo in both tissues. Vitamin E decreased LPS-induced increases in plasma IL-1beta but not IL-6 compared with placebo. The major results provide the first in vivo evidence that short-term vitamin E administration reduces IL-6 and IL-1beta responses to LPS in skeletal and cardiac muscle and prevents LPS-induced increases in NF-kappaB activation and total oxidized proteins.     

Threshold dose of interleukin-1β for induction of an ACTH response is higher than of a febrile response

The present study was carried out to compare the threshold doses of interleukin-1 (IL-1) necessary to elicit febrile and adrenocorticotrophic hormone (ACTH) responses. The results show that intravenous injection of a small dose of IL-1 (0.2 g/kg) did not stimulate ACTH secretion but induced a significant febrile response. How-ever, intravenous injection of a higher dose of IL-1 (2.0 g/kg) induced significant increases in plasma ACTH accompanying the fever. These results suggest that the rise in body temperature per se is not responsible for the ACTH response and that the threshold dose of IL-1 to induce the ACTH response is higher than that to elicit the febrile response.     

Leukotriene and prostaglandin sensitization of cutaneous high-threshold C- and A-delta mechanonociceptors in the hairy skin of rat hindlimbs

Single C- and A-delta fibers were isolated from dissected filaments of the saphenous nerve in pentobarbital anesthetized rats and the corresponding cutaneous receptive fields mapped with calibrated von Frey hairs. Nociceptors were characterized by their responses to noxious mechanical, thermal and chemical stimuli, including intradermal injections of leukotriene B4, prostaglandin E2, bradykinin and capsaicin. Leukotriene B4 decreased the mean mechanical threshold by a maximum of 80% within 10 min and for more than 3 h after intradermal injection of 75 ng of leukotriene B4. The degrees of sensitization of a fiber by leukotriene B4 and prostaglandin E2 were highly correlated. A potentiation effect also was observed, in that injection of prostaglandin E2 or leukotriene B4 1 h after the other eicosanoid further lowered the mechanical threshold of a sensitized fiber, whereas fibers that were not sensitized by leukotriene B4 were unaffected by prostaglandin E2. The sensitizing action of leukotriene B4 and prostaglandin E2 was directed to multiple classes of cutaneous nociceptors including 73% of C-polymodal, 60% of C-mechano-heat, 42% of C-mechano-cold nociceptors and 70% of A-delta high-threshold mechanonociceptors. The pain-evoking substances bradykinin and capsaicin activated 81% and 88%, respectively, of the sensitized C-polymodal nociceptors, 17% and 84% of the sensitized-C-mechano-heat nociceptors, 12% and 37% of the sensitized C-mechano-cold nociceptors, and 17% and none of the sensitized A-delta high-threshold mechanociceptors. The responses of C-fibers to bradykinin and capsaicin were highly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Activation of sensory nerves participates in stress-induced histamine release from mast cells in rats

To elucidate the mechanism by which stress induces rapid histamine release from mast cells, Wistar rats, pretreated as neonates with capsaicin, were subjected to immobilization stress for 2 h, and histamine release was measured in paws of anesthetized rats by using in vivo microdialysis after activation of sensory nerves by electrical or chemical stimulation. Immobilization stress studies indicated that in control rats stress induced a 2.7-fold increase in the level of plasma histamine compared to that in freely moving rats. Whereas pretreatment with capsaicin significantly decreased stress-induced elevation of plasma histamine. Microdialysis studies showed that electrical stimulation of the sciatic nerve resulted in a 4-fold increase of histamine release in rat paws. However, this increase was significantly inhibited in rats pretreated with capsaicin. Furthermore, injection of capsaicin into rat paw significantly increased histamine release in a dose-dependent manner. These results suggest that activation of sensory nerves participates in stress-induced histamine release from mast cells.     

Weight gain and food intake in corticotropin releasing factor immunized Zucker rats

In Zucker obese rats (fa/fa) there are disturbances in the regulation of ACTH and corticosterone. In addition, beta-endorphin concentrations are higher in the pituitary and hypothalamus in obese than in lean rats. Since ACTH and beta-endorphin are thought to be controlled by corticotropin releasing factor (CRF), these effects may be due to abnormalities in CRF regulation. This possibility was investigated by immunizing rats against CRF. Obese rats immunized against CRF developed higher titer antibodies than lean rats. Hypothalamic CRF concentrations were higher in CRF-immunized obese but not lean rats compared with those of control rats, suggesting that compensation for sequestration of peripheral CRF developed in obese rats. In obese, but not lean rats, immunization against CRF decreased weight gains during weeks 1-4 and increased gains during weeks 9-12 and food intakes were decreased during weeks 5-8 compared with those for obese rats immunized against bovine serum albumin (BSA). Adrenal glands weighed 30% less in both obese and lean rats immunized against CRF compared with those immunized against BSA. These responses to immunization against CRF occurred even though plasma, hypothalamic and pituitary concentrations of ACTH and beta-endorphin were unaffected at the end of the study.     

Sympathetic modulation of activity in Adelta- and C-primary nociceptive afferents after intradermal injection of capsaicin in rats

Neuropathic and inflammatory pain can be modulated by the sympathetic nervous system. In some pain models, sympathetic postganglionic efferents are involved in the modulation of nociceptive transmission in the periphery. The purpose of this study is to examine the sensitization of Adelta- and C-primary afferent nociceptors induced by intradermal injection of capsaicin (CAP) to see whether the presence of sympathetic efferents is essential for the sensitization. Single primary afferent discharges were recorded from the tibial nerve after the fiber types were identified by conduction velocity in anesthetized rats. An enhanced response of some Adelta- and most C-primary afferent fibers to mechanical stimuli was seen in sham-sympathectomized rats after CAP (1%, 15 mul) injection, but the enhanced responses of both Adelta- and C-fibers were reduced after sympathetic postganglionic efferents were removed. Peripheral pretreatment with norepinephrine by intraarterial injection could restore and prolong the CAP-induced enhancement of responses under sympathectomized conditions. In sympathetically intact rats, pretreatment with an alpha(1)-adrenergic receptor antagonist (terazosin) blocked completely the enhanced responses of C-fibers after CAP injection in sympathetically intact rats without significantly affecting the enhanced responses of Adelta-fibers. In contrast, a blockade of alpha(2)-adrenergic receptors by yohimbine only slightly reduced the CAP-evoked enhancement of responses. We conclude that the presence of sympathetic efferents is essential for the CAP-induced sensitization of Adelta- and C-primary afferent fibers to mechanical stimuli and that alpha(1)-adrenergic receptors play a major role in the sympathetic modulation of C-nociceptor sensitivity in the periphery.     

Effects of prostaglandin E2, analogs, fatty acids, and indomethacin on fibrinogen level.

Dose-response relations in rabbits for 3-h intravenous infusion of prostaglandin E2 (PGE2) and (15S)-15-methyl-1-prostaglandin E2 methyl ester (MePGE2) on plasma fibrinogen and systolic blood pressure were determined and described by regression equations. MePGE2 was 20 times more active than PGE2. Fibrinogen synthetic rate responses to PGE2 and MePGE2 were estimated. Infusion of the PGE2 precursor, arachidonic acid, elevated plasma fibrinogen, but fibrinogen response to 0.5-9 mg/kg arachidonic acid was unrelated to dose and half that given by 3 mg/kg PGE2. Slow infusion of several other fatty acids raised plasma fibrinogen as effectively as arachidonic acid, but prostaglandins D2 and F2alpha had only a slight effect. Infusion of 30 times the indomethacin dose that blocks platelet prostaglandin synthetase did not alter the plasma fibrinogen response to arachidonic acid. Indomethacin did not inhibit plasma fibrinogen elevations following ACTH or endotoxin infusion, or subcutaneous turpentine injection. Intravenous infusion of two cyclic ether prostaglandin endoperoxide analogs, (15S)-hydroxy-9alpha, 11alpha-(epoxymethano) prosta-5Z, 13E-dienoic acid, and (15S)-hydroxy-11alpha, 9alpha(epoxymethano) prosta-5Z, 13E-dienoic acid, failed to increase plasma fibrinogen.     

Effect of interleukin-1 on adrenocortical activity in intact and hypothalamic deafferentated male rats

Summary The present study was designed to elucidate the site of action of interleukin 1 (IL-1) modulation of the hypothalamic-hypophyseal-adrenal (HHA) axis. An intraperitoneal injection of recombinant human IL-1 (160 U/rat) significantly elevated serum levels of ACTH and corticosterone (CS). In rats with complete mediobasal hypothalamic deafferentation, the HHA response to IL-1 was inhibited. An intracerebroventricular injection of rIL-1 (2 U/ rat) caused a marked increase in serum ACTH and CS. These results suggest that IL-1 activates the HHA axis by a direct effect upon the brain, and that intact neural connections between the mediobasal hypothalamus and extrahypothalamic brain regions are essential for IL-1-induced HHA responses.     

What roles does the organum vasculosum laminae terminalis play in fever in rabbits?

Experiments were designed to clarify the role of the brain's organum vasculosum laminae terminalis (OVLT) in the development of fever in rabbits. Rectal and ear skin temperatures were recorded in conscious animals in which the OVLT had been electrolytically destroyed or in which the preoptic anterior hypothalamus (PO/AH) had been transected bilaterally. When the OVLT had been ablated the febrile responses to intravenous injection of interleukin-1 beta (IL-1β) or tumour necrosis factor alpha were significantly attenuated, while those to intracerebroventricular injection of IL-1β were not affected. Fever induced by intracerebroventricular injection of prostaglandin E₂ (PGE₂) was prolonged significantly. The febrile responses to intravenous injection of IL-1β and to intracerebroventricular injection of PGE₂ were attenuated when the transection was located caudally to the anterior wall of the third ventricle and extended laterally more than about 3 mm in the ventricular wall. The results show that the OVLT region is a site through which signals to increase body temperature are transferred from the blood to the brain in rabbits.