Systemic but not central administration of tumor necrosis factor-alpha attenuates LPS-induced fever in rats

Klir, J. J.; McClellan, J. L.; Kozak, Wiesław; Szelényi, Zoltán; Wong, Grace; Kluger, Matthew J.

doi:10.1152/ajpregu.1995.268.2.r480

Cited by 30 publications

(33 citation statements)

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“…Studies on the role of endogenous TNF in the febrile response to bacterial pyrogens (see Introduction) and other inflammatory stimuli (Cooper et al 1994;Leon et al 1997) indicate distinct reactions depending on the investigated species of experimental animal, and on the exogenous stimulus for the induction of the acute-phase response. In contrast to a number of studies in rats and mice (Long et al 1990;Klir et al 1995;Kozak et al 1995;Takahashi, Brouckaert & Fiers, 1995), our previous experiments support the view that TNF is a pyrogenic substance in guinea-pigs. This view is based on the following observations.…”

Section: Discussioncontrasting

confidence: 95%

Neutralization of pyrogen‐induced tumour necrosis factor by its type 1 soluble receptor in guinea‐pigs: effects on fever and interleukin‐6 release

Roth¹,

Martin²,

Störr³

et al. 1998

The Journal of Physiology

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A soluble form of the tumour necrosis factor (TNF) type 1 receptor (referred to as TNF binding protein, TNF‐bp) at a dose of 1 mg per animal, or an equivalent volume of solvent, was injected together with 10 μg kg−1 lipopolysaccharide (LPS) or 50 μg kg−1 muramyl‐dipeptide (MDP) directly into the arterial circulation of guinea‐pigs and the effects on circulating TNF or interleukin‐6 (IL‐6) and on abdominal temperature were studied. At 15 or 60 min after injection, LPS‐induced and MDP‐induced circulating TNF was below the detection limit of the assay and thus completely neutralized in animals treated with TNF‐bp. In the control group, TNF was still below the limit of detection in most animals 15 min after LPS was injected; in some animals small traces of TNF could already be detected at that time. However, 60 min after administration of LPS, large amounts of TNF (19508 ± 4682 pg ml−1) were measured in the control group. MDP‐induced TNF in plasma was below the limit of detection 15 min after MDP was injected, and rose to 10862 ± 3029 pg ml−1 60 min after injection. Low levels of circulating IL‐6 (20‐40 international units (IU) ml−1) were measured in all groups of animals 15 min after injection of LPS or MDP. This value corresponds to the baseline activity of IL‐6 in plasma of guinea‐pigs. One hour after administration of LPS, IL‐6 rose to 5442 ± 1662 IU ml−1 in the control group and to a significantly lower value of 1485 ± 179 IU ml−1 in guinea‐pigs treated with TNF‐bp. One hour after injection of MDP, circulating IL‐6 was 2614 ± 506 IU ml−1 in the control group, while the corresponding value in animals treated with TNF‐bp again was significantly lower (873 ± 312 IU ml−1). The second phase of the characteristic biphasic LPS fever in guinea‐pigs was significantly attenuated in animals treated with TNF‐bp. The shorter first phase of the febrile response to LPS was identical in both groups of animals. The late phase of MDP‐induced fever (7‐22 h after injection) was depressed by treatment with TNF‐bp, while the first phase of MDP‐induced fever (0‐7 h after injection) was significantly enhanced by the neutralization of TNF by TNF‐bp.

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Section: Discussioncontrasting

confidence: 95%

Neutralization of pyrogen‐induced tumour necrosis factor by its type 1 soluble receptor in guinea‐pigs: effects on fever and interleukin‐6 release

Roth¹,

Martin²,

Störr³

et al. 1998

The Journal of Physiology

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“…We therefore used TNF bp to obtain information about the role of TNF in the long-term responses of rats after a challenge with a high dose of LPS. Special attention was directed to the effects of TNF neutralization on LPS-induced body temperature changes, since the role of TNF in fever remains controversial [4,17,18,19,22,30,32,34].…”

Section: Introductionmentioning

confidence: 99%

The role of tumor necrosis factor (TNF) in the febrile and metabolic responses of rats to intraperitoneal injection of a high dose of lipopolysaccharide

Töllner

Roth

Störr

et al. 2000

Pflugers Arch - Eur J Physiol

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The role of tumor necrosis factor (TNF) in the febrile and metabolic responses of rats to intraperitoneal injection of a high dose of lipopolysaccharide Injection of a high dose of lipopolysaccharide (LPS) induces a septic-shock-like state, which can be accompanied by phases of hypothermia and phases of fever. In the present study we monitored body core temperature and locomotor activity, both by remote radiotelemetry, as well as changes in food intake, body mass and water intake for 3 days after an intraperitoneal (i.p.) injection of a high dose of LPS (5 mg/kg) along with sterile 0.9% saline or a neutralizing form of the soluble tumor necrosis factor (TNF) type 1 receptor (referred to as TNF-binding protein, TNF bp). Intraperitoneal injection of LPS rapidly induced high concentrations of TNF in the plasma and peritoneal lavage fluid. TNF was undetectable in the plasma and peritoneal lavage fluid of animals co-injected with LPS and TNF bp, implying neutralization of peripheral bioactive TNF. Administration of LPS induced hypothermia by about 1.5 degrees C, which lasted for 5 h after injection. During the light-time periods of days 2 and 3 after injection, the rats developed a robust fever. Treatment with TNF bp resulted in a faster recovery from the LPS-induced hypothermia so that the rats developed a pronounced fever on the day of injection. Locomotor activity during night-time periods was suppressed in LPS-treated animals. The LPS-induced depression of night-time activity was not antagonized by co-injection of TNF bp. On day 1 after the injection of LPS, food intake reduced to virtually zero, water intake fell to about 30% of the control value and body mass dropped by 25 g (about 10% of total body mass). With the exception of body mass, these variables recovered slowly during days 2 and 3 after LPS injection, but did not reach the control values. The LPS-induced decreases in food intake, body mass and water intake were significantly attenuated by the treatment with TNF bp. These results confirm that TNF contributes significantly to the rats' responses to intraperitoneal injection of a high dose of LPS. The fact that treatment with TNF bp accelerated and improved the rats' ability to develop a febrile response supports the view that the fever is beneficial, since all other metabolic responses measured in this study were normalized more effectively in those rats that developed a faster and more pronounced increase in body temperature.

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“…The exact role of these cytokines in the production and regulation of the hyperthermic response remains to be elucidated. Central nervous system IL-1 and IL-6 have been demonstrated to play a role in the initial production of the fever response [32,33] . TNF-␣ , in contrast, has been demonstrated to regulate the magnitude of the thermoregulatory response to sepsis, even potentially serving as an anti-pyretic.…”

Section: Discussionmentioning

confidence: 99%

“…TNF-␣ , in contrast, has been demonstrated to regulate the magnitude of the thermoregulatory response to sepsis, even potentially serving as an anti-pyretic. At physiological levels, TNF-␣ acts as an anti-pyretic, limiting sepsis or LPS-induced fever via peripheral mechanisms [32,33] . Additionally, administration of TNF-␣ -soluble receptors can prevent hypothermic responses to LPS [34] .…”

Section: Discussionmentioning

confidence: 99%

Sympathetic Modulation of the Host Defense Response to Infectious Challenge during Recovery from Hemorrhage

Whitaker

Su²,

Walker³

et al. 2010

Neuroimmunomodulation

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Background: Trauma/hemorrhage (TxHem) is associated with an immediate pro-inflammatory response that, if exaggerated or prolonged, is thought to contribute to the subsequent immunosuppression that characterizes the period after injury. Previously we have demonstrated that chemical sympathectomy (SNSx) accentuates this immediate pro-inflammatory response to TxHem. These findings suggest that the noradrenergic system plays a critical role in limiting the magnitude of the inflammatory response during TxHem and preserving the integrity of the host defense response to a subsequent infectious challenge during the period after TxHem. Objective: To examine the contribution of tissue norepinephrine to the host defense response to an infectious challenge during recovery from TxHem. Methods: Male Sprague-Dawley rats underwent SNSx (6-hydroxydopamine, i.p. daily for 3 days) prior to vascular catheter implantation. Conscious, unrestrained rats were subjected to traumatic injury (muscle crush) prior to a fixed-pressure hemorrhage (40 mm Hg for 60 min) and fluid resuscitation followed 24 h later by cecal ligation and puncture (CLP). Results: SNSx impaired the hemodynamic and thermoregulatory response to hemorrhage as indicated by decreased basal blood pressure, impaired blood pressure recovery during fluid resuscitation, and greater hypothermia after CLP. Furthermore, SNSx accentuated the TNF-α, IL-1, IL-6, and IL-10 response to TxHem + infection in plasma 6 h after CLP and in peritoneal lavage fluid 24 h after CLP. Conclusion: These results indicate that the integrity of the noradrenergic system is necessary for adequate hemodynamic, thermoregulatory, and inflammatory responses to infection during the period following TxHem.

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Systemic but not central administration of tumor necrosis factor-alpha attenuates LPS-induced fever in rats

Cited by 30 publications

References 0 publications

Neutralization of pyrogen‐induced tumour necrosis factor by its type 1 soluble receptor in guinea‐pigs: effects on fever and interleukin‐6 release

Neutralization of pyrogen‐induced tumour necrosis factor by its type 1 soluble receptor in guinea‐pigs: effects on fever and interleukin‐6 release

The role of tumor necrosis factor (TNF) in the febrile and metabolic responses of rats to intraperitoneal injection of a high dose of lipopolysaccharide

Sympathetic Modulation of the Host Defense Response to Infectious Challenge during Recovery from Hemorrhage

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