Biomedical subjects

J M Krueger

Publications and source records attributed to J M Krueger.

12 recordsLinked to original sources

PubMed1992

Interleukin 1 receptor antagonist blocks somnogenic and pyrogenic responses to an interleukin 1 fragment.

Previously it was shown that human interleukin 1 (huIL-1) and a huIL-1 fragment, huIL-1 beta 208-240, are somnogenic and pyrogenic in rabbits. However, the amino acid sequences for IL-1 are species-specific and it was unknown whether rabbit (rb) IL-1 beta 208-240 and rat (rt) IL-1 beta 208-240 were active in their respective species. Furthermore, it was unknown whether these fragments elicited their effects via the IL-1 receptors. Two doses of rbIL-1 beta 208-240 (6.0 and 12.0 nmol) were intracerebroventricularly administered to rabbits. The 6.0-nmol dose had little effect, whereas the 12.0-nmol dose greatly increased non-rapid-eye-movement sleep across a 6-hr recording period and induced a febrile response. Rats injected intracerebroventricularly with rtIL-1 beta 208-240 at dark onset responded to three doses of the peptide (1.2, 2.4, and 4.8 nmol). The 1.2-nmol dose did not greatly affect sleep but did induce a moderate febrile response. The 2.4- and 4.8-nmol doses increased non-rapid-eye-movement sleep across the 12-hr recording period. Maximal brain temperature elevations relative to controls after the 2.4- and 4.8-nmol doses of the peptide were 0.9 +/- 0.2 degrees C and 0.7 +/- 0.2 degrees C, respectively. These responses in both rabbits and rats were completely blocked or significantly attenuated when the animals were pretreated with an IL-1 receptor antagonist. These results suggest that the biological activities of IL-1 beta 208-240 are mediated via the IL-1 beta receptors.

Amino Acid Sequence↗

PubMed1992

Prostaglandins E2 and D2 have little effect on rabbit sleep.

Prostaglandins (PGs) are hypothesized to be involved in sleep regulation; PGE2 and PGD2 are major PGs in the hypothalamus of many species and are proposed to reciprocally promote wakefulness and sleep respectively. PGD2 and PGE2 are also major PGs in rabbit cerebrospinal fluid, yet their effects on rabbit sleep have not heretofore been systematically investigated. We report here that a bolus injection of PGE2 into a lateral cerebral ventricle induces dose-dependent fevers and transient sleep responses in rabbits. PGE2 induces a suppression of sleep of 24 min duration. In contrast, PGD2, across a wide range of doses (0.25-500 nmol) failed to alter sleep; however, at the highest dose it induced fever. We conclude that if PGs are involved in sleep regulation, a chronic stimulation of their production by other sleep factors is necessary.

Animals↗

PubMed1992

Antiserum to prolactin decreases rapid eye movement sleep (REM sleep) in the male rat.

Previous reports suggest that blood-born prolactin (PRL) may selectively promote rapid eye movement sleep (REMS). To study the possible involvement of endogenous PRL in sleep regulation, rats were systemically injected with either antiserum to PRL or normal rabbit serum, and the sleep-wake activity was determined during the subsequent 12-h light cycle. The administration of normal rabbit serum in physiological saline did not alter sleep-wake activity compared to control recordings, whereas the PRL antiserum caused a modest and selective suppression in REMS. Immunoreactive PRL was eliminated from the serial plasma samples obtained between 6 to 11 h after the injection of the antiserum. Brain temperature was not affected by the antiserum. The results indicate that physiological pituitary PRL secretion has a slight REMS-promoting activity in the male rat. It is speculated that an increased release of pituitary PRL or the PRL-like substance previously demonstrated in the brain may significantly stimulate REMS.

Animals↗

PubMed1992

The role of double-stranded RNA in induction of the acute-phase response in an abortive influenza virus infection model.

The inducer of the acute-phase response in "flu-like" viral infections is not defined. The hypothesis that virus-associated double-stranded (ds) RNA serves this function was investigated by comparison of several acute-phase responses (fever and sleep patterns, white and nucleated red blood cell levels, serum antiviral activity and ceruloplasmin) induced by the synthetic dsRNA polyriboinosinic:polyribocytidylic acid (poly[rI:rC]) with those induced by influenza virus in rabbits. The capacity of either dsRNA or influenza virus to induce hyporesponsiveness with respect to these acute-phase parameters upon rechallenge with the same agent or cross-challenge 24 h later was also examined. Poly(rI:rC) induced only minimal hyporesponsiveness to itself but was a potent inducer of hyporesponsiveness to virus with respect to fever, sleep, leukograms, and antiviral activity. Therefore, poly(rI:rC) can substitute for virus in terms of induction of acute-phase hyporesponsiveness, suggesting that dsRNA of viral origin triggers the acute-phase response in this model of influenza.

Acute-Phase Reaction↗

PubMed1992

Interactions of cytokines with the hypothalamus-pituitary axis.

Major humoral mechanisms include the endocrine and immune systems, and there is substantial literature describing interactions between these systems during infection and inflammatory processes. Within the brain, such interactions are less well known. One major brain function altered during infection and inflammation and by several endocrine hormones is sleep. These changes in sleep provide a useful illustration of the interactions between cytokines and the hypothalamus-pituitary axis (HPA). Experimental evidence is reviewed that illustrates the interaction of cytokines, especially interleukin-1 (IL-1), with the HPA in regard to their effect on sleep. The evidence linking IL-1, growth hormone-releasing hormone/growth hormone, and corticotropin-releasing hormone to sleep regulation is reviewed. There is also evidence that shows that these two major sleep-regulatory systems are linked to each other.

Cytokines↗

PubMed1992

Tumor necrosis factor-beta induces sleep, fever, and anorexia.

The enhanced sleep, fever, and anorexia experienced during general infections are attributed to the increased production of cytokines. Cytokines such as interleukin-1 and tumor necrosis factor-alpha (TNF-alpha) have characteristic somnogenic, pyrogenic, and anorectic effects. TNF-beta is closely related to TNF-alpha, and they share common receptors. The effects of TNF-beta on sleep-wake activity, brain temperature (Tbr), and food intake were, however, heretofore unknown. We injected 0.5-200 ng TNF-beta into rabbits intracerebroventricularly (icv) in the light period, and the electroencephalogram, movement, and Tbr were recorded for 6 h from rabbits. The highest dose, 200 ng TNF-beta, induced increases in non-rapid-eye-movement sleep and decreases in rapid-eye-movement sleep accompanied with biphasic febrile responses. Icv injection of 100 ng TNF-beta at dark onset suppressed 12-h and 24-h food intake in rats. These data suggest to us that TNF-beta may belong to the group of endogenous pyrogens/sleep factors.

Animals↗

PubMed1992

Somnogenic, pyrogenic, and anorectic activities of tumor necrosis factor-alpha and TNF-alpha fragments.

Exogenously administered tumor necrosis factor-alpha (TNF-alpha) elicits several symptoms of generalized infections such as fever, increased sleep, and anorexia. The aim of the present work was to localize these effects of TNF-alpha to specific amino acid sequences of the parent molecule by characterizing the in vivo and in vitro activities of several synthetic TNF-alpha fragments. Intracerebroventricular injection of TNF-alpha elicited dose-dependent fevers and increases in non-rapid-eye-movement sleep (NREMS) in rabbits. Four fragments also promoted NREMS and five elicited monophasic fevers. All of the somnogenic fragments share the amino acid sequence 31-36. In rats, TNF-alpha and one of the fragments [TNF-alpha-(69-100)] suppressed 12-h food intake. Furthermore, TNF-alpha increased the expression of the intercellular adhesion molecule-1 and enhanced interferon-gamma-induced HLA-DR expression in human glioblastoma cell line. In contrast, none of the fragments possessed these in vitro activities. Our in vivo results support the concept that there are biologically active regions in the TNF-alpha molecule.

Animals↗

PubMed1992

Growth hormone-releasing hormone antibodies suppress sleep and prevent enhancement of sleep after sleep deprivation.

Previous reports suggest that the hypothalamic growth hormone-releasing hormone (GHRH) promotes sleep, especially non-rapid-eye-movement sleep (NREMS). To evaluate the role of endogenous GHRH in sleep regulation, the effects of antibodies to rat GHRH (GHRH-ab) were studied on normal sleep, brain temperature (Tbr), and GH secretion in experiment I and on enhanced sleep after sleep deprivation in experiment II. In experiment I, affinity-purified GHRH-ab (50 and 200 micrograms) raised in goats and a control goat immunoglobulin G (IgG) preparation were injected intracerebroventricularly (icv) in rats 1 h before the onset of the light cycle, and sleep-wake activity and Tbr were recorded for the next 12 or 23 h. Both doses of GHRH-ab suppressed NREMS and REMS throughout the light cycle. Sleep durations at night were normal. Electroencephalographic (EEG) slow-wave activity, characterized by EEG slow-wave amplitudes, was reduced after GHRH-ab during both the light and the dark cycles. Plasma GH concentrations measured 6-12 h after injection of GHRH-ab (200 micrograms) were diminished. Both the control IgG and GHRH-ab elicited fever. In experiment II, the sleep-wake activity and Tbr of rats were recorded for 24 h in three experimental conditions: base-line with icv injection of IgG, 3-h sleep deprivation with icv IgG injection, and 3-h sleep deprivation with icv GHRH-ab (200 micrograms). After sleep deprivation (+IgG), a prompt increase in EEG slow-wave activity (power density analysis) and late increases in NREMS and REMS durations were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Influenza virus-induced changes in rabbit sleep and acute phase responses.

Systematic investigations of sleep after viral inoculation have not previously been described. In the present study, rabbits were inoculated intravenously (iv) with control allantoic fluid followed by two sequential inoculations of influenza virus at intervals of 24 h. After each i.v. inoculation, sleep and brain temperature (Tbr), as well as leukocyte distributions and serum levels of antiviral activity and ceruloplasmin, were monitored. The first viral inoculation elicited several acute phase responses, including increased non-rapid-eye-movement sleep (NREMS), Tbr, serum antiviral activity, and serum ceruloplasmin levels, as well as neutrophilia and lymphopenia. In contrast to the effects of the first inoculation, after the second inoculation of virus, all these acute phase parameters were diminished or absent (the hyporesponsive state). Inoculation of naive rabbits with heat-inactivated virus was similarly ineffective; however, inoculation of this group of rabbits with viable virus 24 h later did induce full-scale acute phase responses. The possible role of cytokines in mediating the acute phase response after influenza viral challenge is discussed. Results support the hypothesis that sleep is a facet of the acute phase response involved in host defense mechanisms.

Acute-Phase Reaction↗

PubMed1992

Modulation of sleep by cortisone in normal and bacterially infected rabbits.

Infectious disease is known to alter both sleep patterns and hydrocortisone (cortisol) concentrations in rabbits. Moreover, the sleep-altering effects of microbial infections are likely to be mediated via endogenous immune modulators whose actions are attenuated by glucocorticoids. To evaluate the relationships between sleep and glucocorticoids during infectious disease, the effects of cortisone administration (20 mg/kg, im) on sleep were examined before and after inoculation of rabbits with Staphylococcus aureus or Escherichia coli. When administered alone, cortisone did not alter the amount of time spent in slow-wave sleep (SWS) but did reduce electroencephalographic (EEG) slow-wave amplitudes during SWS, the number of bouts of SWS and the amount of time spent in rapid-eye-movement sleep. The duration of individual bouts of SWS was increased after cortisone treatment. Bacterially infected rabbits developed biphasic changes in sleep patterns that were characterized by an initial increase and a subsequent decrease both in SWS time and in EEG slow-wave amplitudes during sleep. Cortisone treatment attenuated these effects in S. aureus-inoculated rabbits. In contrast, cortisone treatment did not alter the initial phase of enhanced sleep in E. coli-inoculated rabbits but did attenuate the subsequent sleep suppression. These data indicate that glucocorticoid administration is associated with an attenuated sleep response in bacterially inoculated rabbits.

Animals↗

PubMed1978

Sleep-promoting factor S: purification and properties.

Sleep-promoting factor was purified from acid/acetone extracts of whole brains of rabbits and from brainstems of slaughterhouse cattle. Intraventricular infusion of extracts purified by means of ion exchange and gel filtration induced excess slow-wave sleep in rabbits for 5-10 hr. The procedure is simple and provides material suitable for physiological studies. Further treatment by partition chromatography and electrophoresis yielded an active product that was purified at least 1 million-fold. This product was inactivated by incubation with mixed carboxypeptidases A and B. Amino acid analysis of acid hydrolysates indicated that the effective dose was less than 150 pmol per rabbit and the original concentration in brain tissue was of the order of 30 pmol/g of brain.

Animals↗

PubMed1976

Biochemical studies of tast sensation. Binding of L-[3H]alanine to a sedimentable fraction from catfish barbel epithelium.

Large numbers of taste buds are distributed over the body surface of the channel catfish ictalurus punctatus, with the barbels having an especially high density. L-Alanine, as well as certain other amino acids, are taste stimuli in this animal. Epithelial tissue obtained by gentle scraping of the barbel surface was fractionated by differential centrifugation. A sedimentable fraction (P2) was prepared that was enriched in L[OH]alanine binding activity, the plasma membrane marker enzyme 5'-nucleotidase, and the mitochondrial marker succinate cytochrome c reductase, but not the microsomal marker NADH cytochrome c redu.ctase. Binding of L-[OH]alanine was measured using a Millipore filter method in which correction for non-specific binding was also determined. Time, temperature, and pH for measuring binding activity were established. At the optimal pH of 7.8, the KD for L-alanine is 4.8 X 10(-6) M. The first order dissociation rate constant at 6 degrees is 3.8 X 10(-4) s-1 and at 24 degrees it is 12.1 X 10(-4) s-1. The second order rate constant for association is between 10(2) and 10(3) M-1 S-1. Reversibility of the binding interaction was also demonstrates by the rapid displacement of bound L-[3H]alanine by a large excess of unlabeled L-alanine. That the binding does not represent incorporation into protein was confirmed by the lack of effect of puromycin. The amounts bound of several other chemostimulatory amino acids werealso determined.

Alanine↗