Fever: Role of Pyrogens and Cryogens

Kluger, Matthew J.

doi:10.1152/physrev.1991.71.1.93

Cited by 1,132 publications

(774 citation statements)

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“…E levated body temperatures associated with fever have been proposed to have a major impact on immune responses during infections, as fever influences the clonal expansion and proliferation of lymphocytes and enhances the lymphocyte-mediated cytotoxicity in target cells (1)(2)(3). The persistence of lymphocyte populations in turn will be determined by the balance of death and survival-promoting factors in the cells.…”

Section: Fever-like Hyperthermia Controls T Lymphocyte Persistence Bymentioning

confidence: 99%

Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort

Meinander

Söderström

Kaunisto

et al. 2007

The Journal of Immunology

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Fever has a major impact on immune responses by modulating survival, proliferation, and endurance of lymphocytes. Lymphocyte persistence in turn is determined by the equilibrium between death and survival-promoting factors that regulate death receptor signaling in these cells. A potential integrator of death receptor signaling is the caspase-8 inhibitor c-FLIP, the expression of which is dynamically regulated, either rapidly induced or down-regulated. In this study, we show in activated primary human T lymphocytes that hyperthermia corresponding to fever triggered down-regulation of both c-FLIP-splicing variants, c-FLIPshort (c-FLIPS) and c-FLIPlong, with consequent sensitization to apoptosis mediated by CD95 (Fas/APO-1). The c-FLIP down-regulation and subsequent sensitization was specific for hyperthermic stress. Additionally, we show that the hyperthermia-mediated down-regulation was due to increased ubiquitination and proteasomal degradation of c-FLIPS, the stability of which we have shown to be regulated by its C-terminal splicing tail. Furthermore, the induced sensitivity to CD95 ligation was independent of heat shock protein 70, as thermotolerant cells, expressing substantially elevated levels of heat shock protein 70, were not rescued from the effect of hyperthermia-mediated c-FLIP down-regulation. Our findings indicate that fever significantly influences the rate of lymphocyte elimination through depletion of c-FLIPS. Such a general regulatory mechanism for lymphocyte removal has broad ramifications for fever-mediated regulation of immune responses.

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Section: Fever-like Hyperthermia Controls T Lymphocyte Persistence Bymentioning

confidence: 99%

Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort

Meinander

Söderström

Kaunisto

et al. 2007

The Journal of Immunology

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“…As previously stated, elevated core body temperatures in the febrile range have been associated with improved survival in homeotherms and poikilotherms; however, alterations in the immune system during thermal stress were largely undefined. Feverrange thermal stress has previously been shown to increase lymphocyte priming, proliferation, and cytotoxicity [2,21,23]. WBH also shortens the time to generate an immune response by stimulating the migration of skin-derived dendritic cells (i.e., Langerhans cells) to lymph nodes where they colocalize with arriving T lymphocytes [21,24].…”

Section: Enhanced Lymphocyte-endothelial Interactions With Hyperthermiamentioning

confidence: 99%

Primary immune surveillance: some like it hot

et al. 2007

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The thermal element of fever has been found to be beneficial in models of infectious disease. The contributions of fever-range temperatures to the efficacy of the adaptive immune response have only begun to be delineated. There is accumulating evidence that fever-range thermal stress bolsters primary immune surveillance of lymph nodes and Peyer patches by augmenting lymphocyte extravasation across specialized vessels termed high endothelial venules. Molecular mechanisms have recently come to light by which the thermal component of fever alone may promote lymphocyte trafficking, and thereby the probability of mounting a defense against microbial infection. Acquired knowledge of the molecular changes associated with thermal stress may allow for the development of novel therapies for a variety of disease processes.

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Section: Antidepressants Produce Various Immunomodulatory Effects Asmentioning

confidence: 99%

“…One aim of the present study was to extend these findings by examining the effects of the SSRI fluoxetine (Prozac) on LPS-induced sickness behavior. Because LPS also produces marked changes in body temperature and activation of the hypothalamus-pituitary-adrenal (HPA) axis (Kluger 1991;Tilders et al 1994), another aim of the present study was to examine the effects of antidepressant treatment on these thermoregulatory and neuroendocrine components of the acute phase response.Some of the effects of antidepressants are probably mediated by a direct action on immune cells. For example, TCAs were found to inhibit spontaneous secretion of IL-2 and IFN ␥ from T-cells, as well as spontaneous and LPS-induced secretion of IL-1 ␤ , IL-6 and TNF ␣ from monocytes (Xia et al 1996).…”

mentioning

confidence: 99%

Effects of Antidepressant Drugs on the Behavioral and Physiological Responses to Lipopolysaccharide (LPS) in Rodents

Yirmiya

Pollak

Barak

et al. 2001

Neuropsychopharmacology

203

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Antidepressants produce various immunomodulatory effects, as well as an attenuation of the behavioral responses to immune challenges, such as lipopolysaccharide (LPS). To explore further the effects of antidepressants on neuroimmune interactions, rats were treated daily with either fluoxetine (Prozac) or saline for 5 weeks, and various behavioral, neuroendocrine, and immune functions were measured following administration of either LPS or saline. Chronic fluoxetine treatment significantly attenuated the anorexia and body weight loss, as well as the depletion of CRH-41 from the median eminence and the elevation in serum corticosterone levels induced by LPS. Chronic treatment with imipramine also attenuated LPS-induced adrenocortical activation. In rats and in mice, which normally display a biphasic body temperature response to LPS (initial hypothermia followed by hyperthermia), chronic treatment with fluoxetine completely abolished the hypothermic response and facilitated and strengthened the hyperthermic response. The effects of antidepressants on the responsiveness to LPS are probably not mediated by their effects on peripheral proinflammatory cytokine production, because LPS-induced expression of TNFSeveral lines of evidence indicate that antidepressants produce various immunomodulatory effects. In depressed patients, the effects of antidepressants are variable and seem to be related to the immune status of the patients at the initiation of the treatment. When depression was associated with immune activation, antidepressants reduced immune function and cytokine secretion. For example, the increased plasma levels of IL-6 during acute depression were normalized by 8-week treatment with fluoxetine (Sluzewska et al. 1995), the increased monocyte counts in depressed patients were reduced following 6-weeks treatment with tricyclic antidepressants (TCAs) (Seidel et al. 1996), and the increased numbers of leukocytes and neutrophils were also reduced by antidepressant treatment (Maes et al. 24 , NO . 5 1997). On the other hand, when immune functions were found to be normal, antidepressants had no immunological effects; for example, chronic moclobemide treatment had no effect on monocytes functions, TNF ␣ production or IFN ␥ levels (Landmann et al. 1997). Moreover, in a study of depressed patients who exhibited immune suppression before treatment, the TCA clomipramine increased the production of IL-1 ␤ , IL-2, and IL-3 (Weizman et al. 1994).In experimental animals, TCAs as well as selective serotonin reuptake inhibitors (SSRIs) produce mainly immune suppression and anti-inflammatory effects. For example, antidepressant treatment in vivo inhibited the increased acute phase response in olfactory bulbectomized rats, a useful animal model of depression (Song and Leonard 1994), reduced the production of interleukin-1 (IL-1) and IL-2 in a chronic mild stress model of depression (Kubera et al. 1996), inhibited immune activation in rats with experimental allergic neuritis (Zhu et al. 1994), and produced anti-inflammatory ...

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Fever: Role of Pyrogens and Cryogens

Cited by 1,132 publications

References 0 publications

Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort

Fever-Like Hyperthermia Controls T Lymphocyte Persistence by Inducing Degradation of Cellular FLIPshort

Primary immune surveillance: some like it hot

Effects of Antidepressant Drugs on the Behavioral and Physiological Responses to Lipopolysaccharide (LPS) in Rodents

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