摘要:

Dynamic changes in sleep in response to infectious challenge are a facet of the acute phase response. Changes in sleep induced by infection seem to be of recuperative value to the host. Furthermore, loss of sleep is associated with changes in immune function. Specific components of microbes such as muramyl peptides or endotoxin from bacteria or double-stranded RNA from virus induce sleep responses. These microbial-induced responses are mediated via enhanced cytokine and hormone production. Interleukin-1, tumor necrosis factor and interferon-αare somnogenic. Interleukin-1-enhanced sleep involves growth hormone-releasing hormone. Microbial-cytokine-altered sleep results from an amplification of physiological sleep mechanisms.

ISSN:1021-7401    

DOI:10.1159/000097142

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

During states of infection and inflammation, systemic interleukin 1 (IL-1) results in clear biological effects mediated through the central nervous system, such as fever, anorexia, and activation of the hypothalamic-pituitary-adreno-cortical axis. Given the multiple central effects of IL-1 in the rat, it would be expected that IL-1 receptors ought to be present in rat brain. However, no previous studies have localized IL-1 receptor or its mRNA in rat brain, possibly due to the fact that interspecies probes were used in previous studies. The recent cloning of the rat IL-1 type-I receptor (IL-1RI) has permitted us to conduct an in situ hybridization study using a species-specific,35S-labeled anti-sense riboprobe to localize IL-1 receptor mRNA in rat brain. We localized IL1-1RI mRNA in the hippocampus, choroid plexus, and cerebellum. At the cellular level we found H-IRI mRNA in low to moderate levels in hippocam-pal neurons and in Purkinje cells of the cerebellar cortex, and in high levels in the endothelium of postcapillary venules and in glial cells surrounding arterioles throughout the brain. This pattern of localization provides support to the concept that IL-1 crosses the blood-brain barrier. Future studies are needed to clarify how the expression of the gene encoding IL-1RI is regulated in brain tissue.

ISSN:1021-7401    

DOI:10.1159/000097143

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Injection of interleukin-1 (IL-1) into the third cerebral ventricle (3V) of conscious rats increases plasma prolactin (PRL) concentration. Nitric oxide (NO) is involved in control of corticotropin-releasing factor (CRF) and luteinizing hormone-releasing hormone (LHRH) release. Consequently, we evaluated its role in the PRL-releasing action of IL-1. In the present experiment, NG-mono-methyl-L-arginine (NMMA) (1 mg in 5μl of 0.9% NaCl (saline)], an inhibitor of NO synthase, or 5μl of saline was microinjected into the 3V of conscious, castrate male rats and blood samples were removed from jugular catheters just prior to and at 10-min intervals after injection. A second injection of NMMA or saline was given 60 min after the first. Five minutes after the injection of NMMA or saline, IL-1α(0.6 pmol in 2μl saline), or an equal volume of saline, was injected into the 3V. Plasma PRL concentrations were increased within 10-20 min after injection of IL-1αand a second pulse of PRL usually occurred at 60-70 min following its injection. The maximal increase in plasma PRL from the initial value in the animals injected with IL-1αwas highly significant, whereas there was no significant increase in the animals injected with NMMA plus IL-1αor in the animals injected with saline or NMMA. The area under the plasma PRL curve was significantly elevated in the animals injected with IL-1αabove that of rats injected; with NMMA plus IL-1αduring the first hour after injection. NMMA transiently slowed the decrease in plasma PRL which occurred after intraventricular injection of saline, but otherwise had no effect. We conclude that IL-la releases PRL by activation of NOergic neurons in the hypothalamus which stimulate the release of PRL-releasing factors or inhibit the release of PRL-inhibiting factors resulting in the stimulation of release of PRL from the lactotrophs. It is unlikely that this effect occurs via a pituitary action of IL-1α.

ISSN:1021-7401    

DOI:10.1159/000097144

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

α-Melanocyte-stimulating hormone (α-MSH1-13), a peptide derived from proopiomelanocortin, has remarkable anti-inflammatory and antipyretic activities. This peptide and a tripeptide that forms the COOH-terminal portion of the molecule (α-MSH11-13; Lys Pro Val) inhibit inflammation when given centrally or peripherally Because of the similarity in their actions, the tripeptide has been presumed to be the amino acid message sequence underlying the effects ofα-MSH1-13. To test the possibility that the two peptides occupy the same receptors, competitive binding experiments were performed with B16 mouse melanoma cells that are known to haveα-MSH1-13receptors. In these experiments,α-MSH1-13did not inhibit binding of a radiolabelledα-MSH1-13analog. This finding suggests thatα-MSH1-13andα-MSH11-13exert their anti-inflammatory/antipyretic/anticytokine effects via stimulation of separate receptors. Becauseα-MSH inhibits the effects of several cytokines including inflammation caused by interleukin (IL)-6 and IL-8, the capacity of these cytokines to compete forα-MSH binding sites was tested. There was no evidence that these proinflammatory cytokines bind toα-MSH receptors on murine melanoma cells. Although further tests with host cells involved in inflammation are required, the latter result is the first evidence that the mechanism of anticytokine action ofα-MSH does not depend upon peptide/cytokine competition for binding sites.

ISSN:1021-7401    

DOI:10.1159/000097145

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

To study whether hemorrhage stimulates interleukin-6 (IL-6) production in conscious rats, 30% of the total blood was withdrawn over 3 min through an indwelling venous catheter and the shedblood was reinfused 1 h later. Plasma adrenocorticotropic hormone (ACTH), corticosterone and IL-6 concentration rapidly increased. Plasma ACTH levels peaked at 10 min and corticosterone and IL-6 peaked at 60 min; all started to decrease after reinfusion. In adrenal-ectomized (ADX) rats with or without a corticosterone pellet implant, there was an inverse relationship between IL6 and corticosterone concentrations, greatest in ADX rats and lowest in ADX rats in which plasma corticosterone was elevated by crushing the implanted pellet. However, the ADX rats in which plasma corticosterone was maintained at normal or slightly elevated levels showed greater IL-6 responses to hemorrhage and elevated basal plasma IL-6 levels compared to sham-operated control rats. Twenty-four hours after hemorrhage/reinfusion, ACTH, corticosterone, and IL-6 responses to i.v. injection of lipopolysaccharide (LPS) were all reduced compared to the non-hemorrhaged animals, indicating that hemorrhage impaired general host defense. Although very high plasma corticosterone concentrations markedly suppressed the IL-6 response to LPS, in ADX rats in which plasma corticosterone was maintained at slightly higher levels than normal, the reduced IL-6 response to LPS in the posthemorrhage period was not reversed, but enhanced. Thus corticosterone has biphasic effects on the IL-6 response to hemorrhage and the response to LPS during the posthemorrhage period, which has important clinical implications with regard to the optimal dose of glucocorticoid for maintaining the host defense response. Although both neuronal and hormonal factors may modulate the IL-6 response to acute stress and the reduced response to LPS during the posthemorrhage period, the precise mechanisms as well as the source of IL-6 which increases in response to stress remain to be investigated.

ISSN:1021-7401    

DOI:10.1159/000097146

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

In freely moving rats with cannulae chronically implanted into the locus coeruleus (LC), the effects of corticotropin-releasing factor (CRF) on electrocortical (ECoG) spectrum power activity and on immune mechanisms (splenocyte mitotic response to concanavalin A, Con A, and lipopolysaccharide, LPS, natural killer cell, NK, activity) were assessed. CRF (100-300 ng) microinfused into the LC produced marked ECoG desynchronization characterized by a significant decrease in total voltage power as well as in power of frequency bands of 0.25-3 and 3-6 Hz. These effects lasted 30-60 min according to the dose. A prior administration of a-helical CRF(9-41) (200 ng into the LC 15 min before) prevented ECoG desynchronization induced by CRF (100 ng). In addition, CRF (100 ng) given into the LC produced a significant decrease 45 min later in the splenocyte proliferative response to Con A and LPS and a significant fall of NK activity. These effects were prevented by prior microinfusion into the same site ofα-helical CRF (200 ng). In conclusion, the present experiments show that CRF given into the LC produces an intense state of ECoG desynchronization accompanied by marked immunodepression and suggest that LC is an important site in the brain through which CRF exerts its immunosuppressive activity.

ISSN:1021-7401    

DOI:10.1159/000097147

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Opioid peptides have been shown by several studies to modulate various parameters of the immune response, but scant experimental findings exist on the role played by specific opioid receptor subtypes in the control of immune mechanisms. This study focuses on the in vitro influences of [Trp4,Asn7]der-morphin, aμ-selective agonist, [D-Ala2]deltorphin I, aδ-selective agonist and U50,488, aκ-selective agonist, on the proliferative response of splenocytes to concanavalin A (Con A). [Trp4, Asn7]dermorphin at low concentrations (10–11and 10-12M)enhanced the proliferative response to Con A, whereas higher concentrations (10–6to 10–7M) inhibited it. Both effects were antagonized by naloxone. [D-Ala2]deltorphin I at very low concentrations (10–12to 10–13M) also produced a significant increase in the proliferative response of splenocytes to Con A. This effect was significantly antagonized by natrindole, a specific δ-receptor antagonist. Finally U50,488 at concentrations ranging from 10–8to 10–9Minhibited the proliferative response to Con A. The effects of U50,488 were mediated by the stimulation of theκ-opioid receptors, since a preincubation of splenocytes with the selective antagonist norbinaltorphimine significantly reduced or abolished the U50,488-induced suppression of the mitotic response. In conclusion, our results clearly indicate that the different opioid receptor subtypes play a different role in the control of immune mechanisms and suggest that immunoenhancing effects of opioid peptides are very likely due to the stimulation of μ- and δ-receptors, whereas the immunosuppressive effects are mediated through the stimulation ofκ-opioid receptors.

ISSN:1021-7401    

DOI:10.1159/000097148

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1021-7401    

DOI:10.1159/000097149

出版商:S. Karger AG    

年代:1994

数据来源: Karger