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H Laburn

Publications and source records attributed to H Laburn.

At least 19 recordsLinked to original sources
PubMed1999

The role of tumour necrosis factor-alpha (TNF-alpha) in fever and the acute phase reaction in rabbits.

We investigated the role of tumour necrosis factor-alpha (TNF-alpha) in fever and the acute phase reaction using a specific type-IV phosphodiesterase inhibitor, rolipram, that inhibits the production of TNF-alpha. The body temperatures and serum iron concentrations of rabbits were measured following injections of lipopolysaccharide (LPS) or Staphylococcus aureus (S. aureus) with either rolipram, diclofenac sodium or the appropriate control solutions. Rolipram significantly (P<0.05) inhibited the first phase of both LPS and Staphylococcal fever, but had no effect on the second phase. The fall in serum iron concentration was not significantly affected by the injection of rolipram together with LPS or S. aureus. These results suggest that TNF-alpha is a pyrogen that plays a role during the first phase of fever, at least. However, TNF-alpha appears not to mediate the fall in serum iron concentration during the acute phase reaction.

Acute-Phase Reaction↗
PubMed1994

Circulating cytokine concentrations and cytokine production by monocytes from newborn babies and adults.

As a possible factor responsible for reduced fever responses in the newborn, we measured plasma cytokine concentrations and cytokine production by neonatal monocytes after lipopolysaccharide or IL (interleukin)-1 alpha stimulation in vitro and compared these data with those obtained from adult plasma and monocytes. Whole blood was collected from afebrile adults (n = 12) and the umbilical cord of normal term infants (n = 12). Plasma and peripheral blood monocytes were prepared by conventional techniques. Significantly lower concentrations of IL-1 alpha, IL-1 beta (P < 0.05, t-test) and IL-6 (P < 0.01, t-test) were found in the plasma of newborn babies compared with that of adults. There was no significant difference in plasma tumour necrosis factor (TNF) concentrations between the adults and newborn babies. Monocytes from newborn babies had the capacity to produce IL-1 alpha and IL-1 beta as readily as adult cells after stimulation with lipopolysaccharide or IL-1 alpha, and produced significantly lower concentrations of TNF and IL-6 than those produced by stimulated adult monocytes (P < 0.01, ANOVA). Our results suggest that the reduced production of IL-6 by monocytes of the newborn during infection could be partly responsible for attenuated fever responses observed in the neonate.

Adult↗
PubMed1993

Interleukin-1 receptor antagonist in newborn babies and pregnant women.

We have investigated the possible role of the interleukin-1 receptor antagonist (IL-1ra) in the attenuated fever response in the newborn. Umbilical cord blood was collected from normal full-term infants (n = 12), and venous blood was obtained from afebrile, non-pregnant adults, of both genders (n = 12) and women in late pregnancy (n = 12). Plasma IL-1ra, and IL-1ra produced in vitro by peripheral blood monocytes stimulated with IL-1 alpha or LPS, were assayed by ELISA. Significantly higher concentrations of IL-1ra (P < 0.01, t test) were found in umbilical cord plasma than in plasma of non-pregnant adults. Furthermore concentrations of IL-1ra in the plasma of women in late pregnancy were significantly higher than in the plasma of neonates and non-pregnant adults (P < 0.01, Mann-Whitney rank-sum test). Neonatal monocytes failed to produce significant amounts of IL-1ra upon stimulation in vitro. The monocytes of pregnant women produced much higher concentrations of IL-1ra than the monocytes of non-pregnant adults (P < 0.01 Mann-Whitney rank-sum test). We speculate that IL-1ra may attenuate the febrile response to Gram-negative pyrogens in women in late pregnancy, and by crossing the placenta, also in the newborn.

Enzyme-Linked Immunosorbent Assay↗
PubMed1992

Fever responses in newborn lambs.

Neonatal lambs failed to respond with an increase in body temperature to i.v. injection of both endotoxin (0.4 microgram/kg), a Gram-negative bacterial pyrogen, and the cell walls of Staphylococcus aureus (1 x 10(9), a Gram-positive bacterial pyrogen. However, the fall in serum iron concentration that normally accompanies injection of both the pyrogens in adults was not attenuated in the neonates. We believe that the central nervous system origin of the fever pathway is suppressed in neonatal lambs.

Animals↗
PubMed1992

Fever response of sheep in the peripartum period to gram-negative and gram-positive pyrogens.

We have measured body temperatures and serum iron concentrations of sheep in the peripartum period following administration of endotoxin and Staphylococcus aureus cell walls. Both the rise in rectal temperature and the fall in serum iron concentration following intravenous injection of S. aureus were the same immediately pre- and postpartum as they were 5 weeks after parturition. The rise in rectal temperature following intravenous endotoxin injection immediately pre- and postpartum was significantly less than that of the same ewes 5 weeks later. However, the fall in serum iron concentration following endotoxin injection was significantly suppressed only prepartum. We conclude that fever is not suppressed in sheep in the peripartum period, but the response to endotoxin is suppressed, through complex processes incidental to the mechanism responsible for the maintenance of gestation and induction of labour.

Animals↗
PubMed1991

Response of body temperature and serum iron concentration to repeated pyrogen injection in rabbits.

We measured body temperature and serum iron concentration after five daily consecutive injections of febrile doses of Salmonella typhosa lipopolysaccharide (0.1 micrograms/kg) and two doses of Staphylococcus aureus cell walls (1 x 10(7) and 5 x 10(7) cells) in rabbits. Tolerance to endotoxin injection, as manifest by a significant attenuation in the body temperature elevation, developed after the first injection of endotoxin. The endotoxin-induced fall in serum iron concentration was attenuated significantly by the 5th day of endotoxin injection. In contrast, no tolerance developed in either the body temperature or serum iron response following repeated daily injections of S. aureus. Rabbits rendered tolerant to endotoxin showed normal febrile and serum iron responses to subsequent S. aureus injection. Rabbits given serial injections of S. aureus, although not tolerant to S. aureus itself, exhibited attenuated body temperature responses but not serum iron responses to endotoxin injection. We suggest that repeated injection of endotoxin diminishes the ability of endotoxin to stimulate endogenous pyrogen (EP) synthesis and/or release, a property not shared by the gram-positive pyrogen S. aureus. However, repeated injection of S. aureus weakens the central endotoxin-EP pathway.

Animals↗
PubMed1991

Effects of alpha-melanocyte stimulating hormone on fever caused by endotoxin in rabbits.

1. We measured the effect of intravenous and intracerebroventricular injections of alpha-melanocyte stimulating hormone (alpha-MSH) on changes in body temperature and serum iron concentration following i.v. injection of endotoxin in rabbits. 2. Intravenous alpha-MSH (2.5 micrograms) significantly reduced both phases of endotoxin fever and attenuated the fall in serum iron concentration which follows endotoxin injection. 3. Intracerebroventricular alpha-MSH (200 ng) reduced only the second phase of the fever and had no effect on the fall in the serum iron concentrations. 4. We conclude that alpha-MSH, in doses that are known to inhibit endogenous pyrogen fever, inhibits the fever induced by endotoxin in rabbits, probably by blocking the actions of endogenous pyrogens mediating the endotoxin fever.

Animals↗
PubMed1989

Does heat damage fetuses?

Temperature affects phenotypic variation during critical developmental stages in all forms of life that have been studied thus far. In animal studies of heat teratogenicity, adverse effects have ranged from disruption of the normal cell cycle leading to decreased numbers of cells, to the induction of developmental abnormalities by means of embryonic cell death. The heat shock response is a universal cellular stress reaction in which the transcriptional and translational mechanisms of the cell are pre-empted by preferential induction of heat shock protein synthesis. Occurrence of such a phenomenon during prenatal life could lead to the absence of essential gene products at critical stages of development. The crucial question of whether temperature induced cellular and genetic effects ever occur during human fetal development has been considered only in relation to maternal hyperthermia, which is generally viewed as not being of significance in human teratology. We propose that teratogenicity may result from fetal hyperthermia unrelated to maternal hyperthermia, caused either by impaired fetomaternal heat dissipation due to reduced placental blood flow (extrinsic fetal hyperthermia) or by increased fetal heat production during hypermetabolic states (intrinsic fetal hyperthermia). The need for further studies in this regard is emphasized.

Animals↗
PubMed1987

Pyrogens fail to produce fever in the snakes Psammophis phillipsii and Lamprophis fuliginosus.

1. Preferred body temperature of five diurnal, Psammophis philipsii and three nocturnal, Lamprophis fuliginosus, snakes was measured in a thermal gradient chamber by indwelling colonic thermocouples, before and after injection of a variety of pyrogens. 2. The snakes achieved their preferred body temperature by moving up and down in the gradient chamber; it was about 33 degrees C for P. phillipsii and 25 degrees C for L. fuliginosus. 3. The snakes did not develop fever in response to any of the pyrogens, whether gram-negative or gram-positive in origin, either on the day of injection or on the subsequent day. 4. We believe that fever is rare amongst reptiles.

Animals↗
PubMed1987

Pyrogens fail to produce fever in the leopard tortoise Geochelone pardalis.

1. The body temperature of seven tortoises, Geochelone pardalis, was measured in a thermal gradient chamber, by indwelling thermocouples, after injection of various pyrogens. 2. The tortoises regulated their body temperature by moving in the chamber. 3. The tortoises did not develop fever in response to any of the pyrogens we tested. 4. The results support the contention that fever in reptiles is not ubiquitous.

Animals↗
PubMed1987

Responses of baboons to traditionally pyrogenic agents.

It is not clear whether baboons develop fever in response to endotoxin or other pyrogens. We injected various pyrogens intravenously in 12 unrestrained baboons (Papio ursinus) and measured their body temperature using intra-abdominal radiotelemeters. Serum iron concentration was also measured. The baboons developed fever after injection of killed Staphylococcus aureus (5 X 10(7) organisms/kg). No significant fever was measured after injection of lipopolysaccharide (Salmonella typhosa) (0.1, 8, 40, and 100 micrograms/kg), bovine serum albumin (4 mg/kg), killed Salmonella minnesota (5 X 10(7) organisms/kg), and killed Salmonella typhi (5 X 10(7) organisms/kg). A significant decrease in serum iron concentration was found only after injection of S. aureus and lipopolysaccharide, 100 micrograms/kg. The phagocytic synthesis of interleukin-1 following pyrogen stimulation in baboons and some other primates appears to differ from that in man and in nonprimates.

Animals↗
PubMed1982

On the pyrogenic action of intravenous lipid A in rabbits.

1. Previous evidence purporting to show that lipid A is the pyrogenic moiety of endotoxin is demonstrably inconclusive. 2. We have extracted lipid A from endotoxin of Salmonella typhosa and tested the pyrogenic action of the lipid A, the residual polysaccharide and the parent endotoxin, by intravenous injection in conscious rabbits. 3. Lipid A dissolved in an aqueous solution of rabbit serum albumin induced a significant pyrexia of short latency, while neither rabbit serum albumin alone, nor the polysaccharide from S. typhosa, affected body temperature. The physical presence in the injectate of the polysaccharide from S. typhosa did not enhance the pyrogenicity of the lipid. 4. Dose-response curves for lipid A and the parent endotoxin, over the dose range 10 ng-20 micrograms, showed that lipid A incorporated in endotoxin was much more pyrogenic than pure lipid A in solution. When separated from the polysaccharide component of endotoxin, lipid A lost more than 99.9% of its pyrogenic activity, at threshold doses.

Animals↗
PubMed1980

Effects of intracerebroventricular floctafenine and indomethacin on body temperature in febrile rabbits.

1. We injected the potent prostaglandin synthesis inhibitors, floctafenine and indomethacin, intravenously and intracerebroventricularly in rabbits made febrile by intravenous injection of leucocyte pyrogen. 2. Floctafenine (75 mumol) injected intravenously failed to affect the fever, whereas indomethacin (15 mumol) markedly reduced the fever. 3. When injected into the cerebral ventricles, floctafenine was feebly antipyretic, and then only at a dose ten times the antipyretic dose of indomethacin. 4. Our results support the suggestion that floctafenine has no antipyretic action when administered peripherally. However, its lack of antipyretic effect cannot be explained solely on the grounds that it fails to cross the blood-brain barrier.

Animals↗
PubMed1979

Fever induced in rabbits by intravenous injection of bovine serum albumin.

1. Bovine serum albumin injected into conscious rabbits produced a dose-dependent fever of short latency and duration of at least 2 1/2 hr. 2. The fever was not due to contamination by other proteins nor due to contamination by bacterial endotoxin. 3. The fever following albumin injection had characteristics similar to endogenous pyrogen fever. 4. Some traditional ways of distinguishing bacterial endotoxin fever from other types of fever need to be reassessed.

Animals↗
PubMed1979

Intraventricular microinjections of a stable analogue of prostaglandin endoperoxide cause fever in rabbits.

1. Derivatives of arachidonic acid other than prostaglandin are pyrogenic, the likely candidates being the prostaglandin endoperoxides and/or the thromboxanes. 2. Intraventricular microinjections in rabbits of a stable analogue of prostaglandin endoperoxide resulted in dose-dependent increases of rectal temperature. The pyrexia was delayed in onset; no significant change in body temperature occurred for at least an hour. 3. The pyrexia was unaltered by simultaneous injection of the potent prostaglandin synthetase inhibitor indomethacin. 4. We suggest that both prostaglandins and prostaglandin endoperoxides may be implicated in fever.

Animals↗
PubMed1978

The febrile responses in rabbits and rats to leucocyte pyrogens of different species.

1. We have investigated the effects on body temperature of rats and rabbits of leucocyte pyrogen derived from the blood of rat, rabbit, ox, pig and baboon. 2. In the rabbit intravenous injections (3.5 ml.) of solutions containing leucocyte pyrogen derived from ox, pig and rabbit blood produced fevers with short latencies; no fevers resulted from injections of similar solutions derived from rat or baboon blood. 3. In the rat intraperitoneal injections (2.0 ml.) of solutions containing leucocyte pyrogen derived from ox blood caused a fever, while pig leucocyte pyrogen produced a marked hypothermia. Neither rabbit, baboon, nor rat leucocyte pyrogen had any significant effect on rectal temperature of the rats. 4. Our results show that there is a variability of response in the rat and the rabbit to injection of leucocyte pyrogen of different species; leucocyte pyrogen may be species specific.

Animals↗
PubMed1977

Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits.

1. Sodium arachidonate, the prostaglandin precursor substance, when injected intraventricularly into rabbits, results in dose-dependent hyperthermia, which is rapid in onset and of several hours duration. 2. Arachidonate fever was inhibited by intraventricular injection of indomethacin, but not by the simultaneous intraventricular injection of either of the two prostaglandin antagonists SC 19220 or HR 546. 3. Both antagonists effectively inhibited the fever induced by the intraventricular injection of an equipotent dose of PGE1. 4. Our results show that a derivative of arachidonic acid other than prostaglandin is pyrogenic.

Animals↗