Fever and hypothermia: two adaptive thermoregulatory responses to systemic inflammation

Romanovsky, Andrej A.; Székely, Miklós

doi:10.1016/s0306-9877(98)90022-6

Cited by 141 publications

(119 citation statements)

References 25 publications

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“…Our studies show that LPS-induced fever and hypothermia are both physiological responses brought about by brain-driven changes in thermoeffector activity (3,4,70). Whereas the biological value of fever is thought to be related to its immunostimulant and antibacterial effects (43), the biological value of hypothermia may be related to energy conservation when inflammation is severe enough to compromise tissue perfusion or threaten energy reserves (72,82).…”

mentioning

confidence: 75%

Cyclooxygenase-1 or -2—which one mediates lipopolysaccharide-induced hypothermia?

Steiner

Hunter²,

Phipps³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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DL, Romanovsky AA. Cyclooxygenase-1 or -2-which one mediates lipopolysaccharide-induced hypothermia? Am J Physiol Regul Integr Comp Physiol 297: R485-R494, 2009. First published June 10, 2009 doi:10.1152/ajpregu.91026.2008.-Systemic inflammation is associated with either fever or hypothermia. Fever, a response to mild systemic inflammation, is mediated by cyclooxygenase (COX)-2 and not by COX-1. However, it is still disputed whether COX-2, COX-1, neither, or both mediate(s) responses to severe systemic inflammation, and, in particular, the hypothermic response. We compared the effects of SC-236 (COX-2 inhibitor) and SC-560 (COX-1 inhibitor) on the deep body temperature (Tb) of rats injected with a lower (10 g/kg iv) or higher (1,000 g/kg iv) dose of LPS at different ambient temperatures (Tas). At a neutral Ta (30°C), the rats responded to LPS with a polyphasic fever (lower dose) or a brief hypothermia followed by fever (higher dose). SC-236 (2.5 mg/kg iv) blocked the fever induced by either LPS dose, whereas SC-560 (5 mg/kg iv) altered neither the febrile response to the lower LPS dose nor the fever component of the response to the higher dose. However, SC-560 blocked the initial hypothermia caused by the higher LPS dose. At a subneutral T a (22°C), the rats responded to LPS with early (70 -90 min, nadir) dose-dependent hypothermia. The hypothermic response to either dose was enhanced by SC-236 but blocked by SC-560. The hypothermic response to the higher LPS dose was associated with a fall in arterial blood pressure. This hypotensive response was attenuated by either SC-236 or SC-560. At the onset of LPS-induced hypothermia and hypotension, the functional activity of the COX-1 pathway (COX-1-mediated PGE2 synthesis ex vivo) increased in the spleen but not liver, lung, kidney, or brain. The expression of splenic COX-1 was unaffected by LPS. We conclude that COX-1, but not COX-2, mediates LPS hypothermia, and that both COX isoforms are required for LPS hypotension. body temperature; thermoregulation; fever; inflammation SO STRONGLY IS SYSTEMIC INFLAMMATION associated with changes in deep body temperature (T b ) that every clinical definition of the systemic inflammatory response syndrome includes a change in T b (11,48). Whereas the majority (ϳ90%) of patients with systemic inflammation have an increased T b , a number of them (ϳ10%) have a lowered T b (6, 17). Thermoregulatory manifestations are also present in animal models of systemic inflammation. In a rat model of systemic inflammation induced by bacterial LPS, the pattern of T b change depends on the ambient temperature (T a ) and the LPS dose. At a neutral or supraneutral T a (warm environment), fever is the prevailing response; the fever is monophasic when the dose of LPS is low (just suprathreshold), but it turns polyphasic as the dose increases (66, 68, 69, 71, 79); a mild hypothermia may precede the polyphasic fever when the dose of LPS is high (68). At a subneutral T a (cool environment), hypothermia followed by fever is the predominant response; th...

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mentioning

confidence: 75%

Cyclooxygenase-1 or -2—which one mediates lipopolysaccharide-induced hypothermia?

Steiner

Hunter²,

Phipps³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…For example, elevated T b have been hypothesised to act as a natural defence against bacterial infections in free-living California ground squirrels [Spermophilus beecheyi (Muchlinski et al, 2000)] and captive mice [Peromyscus melanophrys (Martin et al, 2008a)]. Additionally, hypothermia may be a defence against pathogens under conditions of low resource availability (Romanovsky and Szekely, 1998). Thus, hypothermia may be an adaptive response to infection in zebra finches, as hypothesised previously for rodents that originate in regions of low productivity (Martin et al, 2008a).…”

Section: Thermoregulatory Response To Lps and Environmental Temperaturementioning

confidence: 87%

Is there an energetic-based trade-off between thermoregulation and the acute phase response in zebra finches?

Burness

Armstrong

Fee

et al. 2010

Journal of Experimental Biology

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SUMMARYThere has been recent interest in understanding trade-offs between immune function and other fitness-related traits. At proximate levels, such trade-offs are presumed to result from the differential allocation of limited energy resources. Whether the costs of immunity are sufficient to necessitate such energy reallocation remains unclear. We tested the metabolic and behavioural response of male zebra finches (Taeniopygia guttata) to the combined effects of thermoregulation and generation of an acute phase response (APR). The APR is the first line of defence against pathogens, and is considered energetically costly. We predicted that at cold temperatures zebra finches would exhibit an attenuated APR when compared with individuals at thermoneutrality. We challenged individuals with bacterial lipopolysaccharide (LPS), an immunogenic compound that stimulates an APR. Following LPS injection, we measured changes in food intake, body mass, activity, and resting and total energy expenditure. When challenged with LPS under ad libitum food, individuals at both temperatures decreased food intake and activity, resulting in similar mass loss. In contrast to predicted energetic trade-offs, cold-exposed individuals injected with LPS increased their nocturnal resting energy expenditure more than did individuals held at thermoneutrality, yet paradoxically lost less mass overnight. Although responding to LPS was energetically costly, resulting in a 10% increase in resting expenditure and 16% increase in total expenditure, there were few obvious energetic trade-offs. Our data support recent suggestions that the energetic cost of an immune response may not be the primary mechanism driving trade-offs between immune system function and other fitness-related traits.

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“…ON A SYSTEMIC INFLAMMATORY challenge (e.g., with bacterial LPS or pyrogenic cytokines, such as IL-1␤ and TNF-␣), the brain launches a powerful defense response: fever (29,51). Fever is mediated by prostaglandin (PG) E 2 (8).…”

mentioning

confidence: 99%

Expression of genes controlling transport and catabolism of prostaglandin E₂in lipopolysaccharide fever

Ivanov¹,

Scheck

Romanovsky³

2003

American Journal of Physiology-Regulatory, Integrative and Comp

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) E2 is a principal downstream mediator of fever and other symptoms of systemic inflammation. Its inactivation occurs in peripheral tissues, primarily the lungs and liver, via carrier-mediated cellular uptake and enzymatic oxidation. We hypothesized that inactivation of PGE2 is suppressed during LPS fever and that transcriptional downregulation of PGE2 carriers and catabolizing enzymes contributes to this suppression. Fever was induced in inbred Wistar-Kyoto rats by intravenous LPS (50 g/kg); the controls received saline. Samples of the liver, lungs, and hypothalamus were harvested 0, 0.5, 1.5, and 5 h postinjection. The expression of the two principal transmembrane PGE2 carriers (PG transporter and multispecific organic anion transporter) and the two key PGE2-inactivating enzymes [15-hydroxy-PG dehydrogenase (15-PGDH) and carbonyl reductase] was quantified by RT-PCR. All four genes of interest were downregulated in peripheral tissues (but not the brain) during fever. Most remarkably, the expression of hepatic 15-PGDH was decreased 26-fold 5 h post-LPS, whereas expression of pulmonary 15-PGDH was downregulated (as much as 18-fold) throughout the entire febrile course. The transcriptional downregulation of several proteins involved in PGE2 inactivation, first reported here, is an unrecognized mechanism of systemic inflammation. By increasing the bloodbrain gradient of PGE2, this mechanism likely facilitates penetration of PGE2 into the brain and prevents its elimination from the brain. systemic inflammation; multispecific organic anion transporter; prostaglandin transporter; 15-hydroxyprostaglandin dehydrogenase; carbonyl reductase ON A SYSTEMIC INFLAMMATORY challenge (e.g., with bacte-

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Fever and hypothermia: two adaptive thermoregulatory responses to systemic inflammation

Cited by 141 publications

References 25 publications

Cyclooxygenase-1 or -2—which one mediates lipopolysaccharide-induced hypothermia?

Cyclooxygenase-1 or -2—which one mediates lipopolysaccharide-induced hypothermia?

Is there an energetic-based trade-off between thermoregulation and the acute phase response in zebra finches?

Expression of genes controlling transport and catabolism of prostaglandin E₂in lipopolysaccharide fever

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Fever and hypothermia: two adaptive thermoregulatory responses to systemic inflammation

Cited by 141 publications

References 25 publications

Cyclooxygenase-1 or -2—which one mediates lipopolysaccharide-induced hypothermia?

Cyclooxygenase-1 or -2—which one mediates lipopolysaccharide-induced hypothermia?

Is there an energetic-based trade-off between thermoregulation and the acute phase response in zebra finches?

Expression of genes controlling transport and catabolism of prostaglandin E2in lipopolysaccharide fever

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Expression of genes controlling transport and catabolism of prostaglandin E₂in lipopolysaccharide fever