Topic
Fever generation
About: Fever generation is a research topic. Over the lifetime, 28 publications have been published within this topic receiving 2815 citations.
Papers
TL;DR: Before any cytokine or hormone can be characterized as an EP or EC (or, for that matter, as being involved in any of the acute phase responses), clearly established rules must be followed, which are patterned after the traditional criteria used by Koch to distinguish a pathogenic microorganism from a benign one.
Abstract: The biology of cytokines is one of the most rapidly growing areas of biomedical research. It is understandable why the assumption was made several years ago that EP was equivalent to IL-1 (both alpha and beta) and subsequently to IL-1 alpha, IL-1 beta, and TNF. However, as more data have been obtained, it has become clearer that many cytokines and hormones are capable of participating in the febrile response. It is also becoming apparent that EPs and ECs might influence body temperature during nonpathological states, perhaps contributing to the elevation in temperature during or after exercise, the circadian variation in temperature, and others. Medical textbooks have begun to list IL-1 as the EP. As I attempted to make clear in this review, evidence that IL-1 alpha is a circulating EP is poor. The evidence is considerably stronger that IL-1 beta is an EP, at least during LPS-induced fever in rodents. The point I have tried to emphasize is that before any cytokine or hormone can be characterized as an EP or EC (or, for that matter, as being involved in any of the acute phase responses), clearly established rules must be followed, which are patterned after the traditional criteria used by Koch to distinguish a pathogenic microorganism from a benign one. As summarized in Tables 4 and 5, there are many candidates for EPs and ECs, but much more experimental evidence is essential before we gain a clear understanding of the relationship between contact with an exogenous pyrogen, the release of EPs and ECs, and the development of fever.
1,276 citations
TL;DR: This review summarizes the current understanding of cyclooxygenase expression and prostanoid actions in the nervous system, with special reference to COX-2 and studies demonstrating its expression in different cell types responding to a variety of stimuli.
Abstract: In the nervous system, prostanoids are well recognized as mediators in a variety of processes, including fever generation, modulation of the stress response, sleep/wake cycle, control of cerebral blood flow, and hyperalgesia. Two isoforms of cyclooxygenase (COX), the enzyme that catalyzes the conversion of arachidonic acid to prostanoids, are now recognized: a constitutively expressed COX-1 and a highly regulated COX-2. New molecular and pharmacologic tools have provided a better understanding of the roles of COX-generated prostanoids in the nervous system. Other studies reveal that COX may represent an important target for new therapeutic approaches to neurologic disorders. This review summarizes our current understanding of cyclooxygenase expression and prostanoid actions in the nervous system, with special reference to COX-2 and studies demonstrating its expression in different cell types responding to a variety of stimuli. A brief review of the molecular biology, pharmacology, and primary actions of COX-2 outside of the nervous system provides a context for understanding potential neurobiological roles for COX-2 and prostanoid production. Information about the role of COX in human neurological disorders, including cerebrovascular disease, Alzheimer' s disease, and hyperalgesia, is covered in the last section.
409 citations
TL;DR: The findings suggest that during fever or inflammation, renal secretory transport of PGE2 is reduced, contributing to elevated PGE 2 levels in blood, and could explain why increased plasma urate levels occur in diseases that go along with increased levels of P GE2.
Abstract: Prostaglandin E2 (PGE2) is the principal mediator of fever and inflammation. Recently, evidence emerged that during febrile response, PGE2 that is generated in the periphery enters the hypothalamus and contributes to the maintenance of fever. In a rat model of fever generation, peripheral PGE2 is increased, whereas clearance by metabolism of peripheral PGE2 is downregulated. The major route of PGE2 excretion is via the renal proximal tubular organic anion secretory system, where basolateral uptake that is mediated by renal organic anion transporter 1 (rOAT1) and rOAT3 is rate limiting. Therefore, it was hypothesized that PGE2 itself will abolish its excretion by rOAT1 or rOAT3. Fluorescein was used as a prototypic organic anion, and NRK-52E cells from rat served as a proximal tubular model system. PGE2 time-dependently downregulates basolateral organic anion uptake, without affecting cell volume or cell protein, recirculation of counter ions, or proximal tubular transport systems in general. In addition, PGE2 diminishes expression of both rOAT1 and rOAT3. Both organic anion uptake and expression of rOAT1 and rOAT3 are dose-dependently downregulated by PGE2. These findings suggest that during fever or inflammation, renal secretory transport of PGE2 is reduced, contributing to elevated PGE2 levels in blood. These data fit into the hypothetical concept of peripheral PGE2’s playing a significant role in fever. The described regulatory mechanism may also be of relevance in chronic inflammatory events. Moreover, the data presented could explain why increased plasma urate levels occur in diseases that go along with increased levels of PGE2.
52 citations
TL;DR: Results indicate that the central CO-heme oxygenase pathway increases T(b) independently of prostaglandins.
Abstract: Recently, the carbon monoxide (CO)-heme oxygenase pathway has been shown to play an important role in fever generation by acting on the central nervous system, but the mechanisms involved have not ...
52 citations
TL;DR: Results show that fasting does not alter the febrigenic signaling from the periphery to the brain important for central P GE2 synthesis but does affect thermoregulatory mechanisms downstream of and/or independent of central PGE2 action.
Abstract: Acute starvation attenuates the fever response to pathogens in several mammalian species. The underlying mechanisms responsible for this effect are not fully understood but may involve a compromised immune and/or thermoregulatory function, both of which are prerequisites for fever generation. In the present study, we addressed whether the impaired innate immune response contributes to the reported attenuation of the fever response in fasted rats during LPS-induced inflammation. Animals fasted for 48 h exhibited a significant and progressive hypothermia prior to drug treatment. An intraperitoneal injection of LPS (100 μg/kg) resulted in a significantly attenuated fever in the fasted animals compared with the fed counterparts. This attenuation was accompanied by the diminution in the concentration of some [TNF and IL-1 receptor antagonist (RA)] but not all (IL-1β and IL-6) of the plasma cytokines normally elevated in association with the fever response. Nevertheless, fasting had no effect on the LPS-induced inflammatory responses at the level of the brain, as assessed by mRNA expressions of inhibitory factor(I)-κB, suppressor of cytokine signaling (SOCS3), IL-1β, cyclooxygenase (COX)-2, and microsomal PGE synthase (mPGES)-1 in the hypothalamus, as well as by PGE2 elevations in the cerebrospinal fluid. In contrast, fasting significantly attenuated the fever response to central PGE2 injection. These results show that fasting does not alter the febrigenic signaling from the periphery to the brain important for central PGE2 synthesis but does affect thermoregulatory mechanisms downstream of and/or independent of central PGE2 action.
47 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2019 | 1 |
| 2018 | 1 |
| 2017 | 1 |
| 2013 | 1 |
| 2011 | 1 |
| 2010 | 1 |