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Fever and the thermal regulation of immunity: the immune system feels the heat

Evans et al., Nature Reviews Immunology, doi:10.1038/nri3843
May 2015  
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Review of fever and the thermal regulation of immunity. Authors discuss how the evolutionary conservation of fever for over 600 million years argues for a protective role, with the survival benefit outweighing the metabolic cost. Febrile temperatures are proposed to boost innate and adaptive immunity through several mechanisms. These include improving neutrophil bactericidal activity, natural killer cell cytotoxicity, dendritic cell migration and antigen presentation, and lymphocyte trafficking into lymphoid tissues. Interleukin-6 is highlighted as a key mediator of both fever and lymphocyte homing through an endothelial trans-signalling mechanism involving soluble IL-6 receptor alpha. Thermal signals are also implicated in attenuating inflammation during recovery from infection. Additionally, new data reveals overlapping signaling pathways between fever-induced thermogenesis and immune cell function, suggesting tight interplay between temperature regulation and immunity.
Reviews covering thermotherapy for COVID-19 include Cohen, Evans, Kunutsor, Larenas-Linnemann, Mancilla-Galindo, Ramirez.
Evans et al., 15 May 2015, peer-reviewed, 3 authors.
This PaperThermotherapyAll
Fever and the thermal regulation of immunity: the immune system feels the heat
Sharon S Evans, Elizabeth A Repasky, Daniel T Fisher
Nature Reviews Immunology, doi:10.1038/nri3843
Fever is a cardinal response to infection that has been conserved in warm-blooded and cold-blooded vertebrates for more than 600 million years of evolution. The fever response is executed by integrated physiological and neuronal circuitry and confers a survival benefit during infection. In this Review, we discuss our current understanding of how the inflammatory cues delivered by the thermal element of fever stimulate innate and adaptive immune responses. We further highlight the unexpected multiplicity of roles of the pyrogenic cytokine interleukin-6 (IL-6), both during fever induction and during the mobilization of lymphocytes to the lymphoid organs that are the staging ground for immune defence. We also discuss the emerging evidence suggesting that the adrenergic signalling pathways associated with thermogenesis shape immune cell function.
Competing interests statement The authors declare no competing interests.
References
Ager, Isolation and culture of high endothelial cells from rat lymph nodes, J. Cell Sci
Ahn, Thiele, Redox regulation of mammalian heat shock factor 1 is essential for Hsp gene activation and protection from stress, Genes Dev
Akerfelt, Morimoto, Sistonen, Heat shock factors: integrators of cell stress, development and lifespan, Nature Rev. Mol. Cell Biol
Akira, Takeda, Toll-like receptor signalling, Nature Rev. Immunol
Almeida, Steiner, Branco, Romanovsky, Cold-seeking behavior as a thermoregulatory strategy in systemic inflammation, Eur. J. Neurosci
Appenheimer, References 138 and 139 identify an evolutionarily conserved role of IL-6 trans-signalling in enhancing L-selectin-dependent adhesion in lymphocytes during exposure to febrile temperatures, Eur. J. Immunol
Arnouk, Tumour secreted grp170 chaperones full-length protein substrates and induces an adaptive anti-tumour immune response in vivo, Int. J. Hyperthermia
Asea, Novel signal transduction pathway utilized by extracellular HSP70: role of Toll-like receptor (TLR) 2 and TLR4, J. Biol. Chem
Atreya, Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in Crohn disease and experimental colitis in vivo, Nature Med
Bachleitner-Hofmann, Heat shock treatment of tumor lysate-pulsed dendritic cells enhances their capacity to elicit antitumor T cell responses against medullary thyroid carcinoma, J. Clin. Endocrinol. Metab
Basu, Binder, Ramalingam, Srivastava, CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin, Immunity
Becker, Hartl, Wieland, CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes, J. Cell Biol
Benveniste, Sparacio, Norris, Grenett, Fuller, Induction and regulation of interleukin-6 gene expression in rat astrocytes, J. Neuroimmunol
Bernheim, Bodel, Askenase, Atkins, Effects of fever on host defense mechanisms after infection in the lizard Dipsosaurus dorsalis, Br. J. Exp. Pathol
Bernheim, Kluger, Fever: effect of drug-induced antipyresis on survival, Science
Berwin, Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells, EMBO J
Beurel, Jope, Lipopolysaccharide-induced interleukin-6 production is controlled by glycogen synthase kinase-3 and STAT3 in the brain, J. Neuroinflamm
Binder, Srivastava, Essential role of CD91 in re-presentation of gp96-chaperoned peptides, Proc. Natl Acad. Sci. USA
Blanford, Thomas, Adult survival, maturation, and reproduction of the desert locust Schistocerca gregaria infected with the fungus Metarhizium anisopliae var acridum, J. Invertebr. Pathol
Blatteis, Li, Li, Feleder, Perlik et al., PGE 2 and endotoxic fever: a re-assessment, Prostaglandins Other Lipid Mediat
Blattman, Estimating the precursor frequency of naive antigen-specific CD8 T cells, J. Exp. Med
Boscacci, Comprehensive analysis of lymph node stroma-expressed Ig superfamily members reveals redundant and nonredundant roles for ICAM-1, ICAM-2, and VCAM-1 in lymphocyte homing, Blood
Burd, Tumor cell apoptosis, lymphocyte recruitment and tumor vascular changes are induced by low temperature, long duration (fever-like) whole body hyperthermia, J. Cell. Physiol
Cabanac, Fever in the leech, Nephelopsis obscura (Annelida), J. Comp. Physiol. B
Calabrese, Rose-John, IL-6 biology: implications for clinical targeting in rheumatic disease, Nature Rev. Rheumatol
Cannon, Nedergaard, Nonshivering thermogenesis and its adequate measurement in metabolic studies, J. Exp. Biol
Cao, Matsumura, Yamagata, Watanabe, Endothelial cells of the rat brain vasculature express cyclooxygenase-2 mRNA in response to systemic interleukin-1β: a possible site of prostaglandin synthesis responsible for fever, Brain Res
Capitano, Elevating body temperature enhances hematopoiesis and neutrophil recovery after total body irradiation in an IL-1-, IL-17-, and G-CSFdependent manner, Blood
Carman, Springer, A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them, J. Cell Biol
Carman, Springer, Integrin avidity regulation: are changes in affinity and conformation underemphasized?, Curr. Opin. Cell Biol
Carman, Springer, Trans-cellular migration: cell-cell contacts get intimate, Curr. Opin. Cell Biol
Cartmell, Poole, Turnbull, Rothwell, Luheshi, Circulating interleukin-6 mediates the febrile response to localised inflammation in rats, J. Physiol
Celsus, Cornelius, Celsus of Medicine: in Eight Books
Chai, Gatti, Toniatti, Poli, Bartfai, Interleukin (IL)-6 gene expression in the central nervous system is necessary for fever response to lipopolysaccharide or IL-1β: a study on IL-6-deficient mice, J. Exp. Med
Chen, Central role of IL-6 receptor signaltransducing chain gp130 in activation of L-selectin adhesion by fever-range thermal stress, Immunity
Chen, Hsp70 inhibits lipopolysaccharideinduced NF-κB activation by interacting with TRAF6 and inhibiting its ubiquitination, FEBS Lett
Chu, Dupuy, Thermal ablation of tumours: biological mechanisms and advances in therapy, Nature Rev. Cancer
Cooper, Febrile-range temperature modifies cytokine gene expression in LPS-stimulated macrophages by differentially modifying NF-κB recruitment to cytokine gene promoters, Am. J. Physiol. Cell Physiol
Covert, Reynolds, Survival value of fever in fish, Nature
Dantzer, Wollman, Molecular mechanisms of fever: the missing links, Eur. Cytokine Netw
Dewhirst, Landon, Hofmann, Stauffer, Allison et al., Novel approaches to treatment of hepatocellular carcinoma and hepatic metastases using thermal ablation and thermosensitive liposomes, Surg. Oncol. Clin. N. Am
Di, Repasky, Subjeck, Distribution of HSP70, protein kinase C, and spectrin is altered in lymphocytes during a fever-like hyperthermia exposure, J. Cell. Physiol
Earn, Andrews, Bolker, Population-level effects of suppressing fever, Proc. Biol. Sci
Elander, Ruud, Korotkova, Jakobsson, Blomqvist, Cyclooxygenase-1 mediates the immediate corticosterone response to peripheral immune challenge induced by lipopolysaccharide, Neurosci. Lett
Elenkov, Wilder, Chrousos, Vizi, The sympathetic nerve-an integrative interface between two supersystems: the brain and the immune system, Pharmacol. Rev
Ellis, but not corticosterone, mediates circulating neutrophilia induced by febrile-range hyperthermia, J. Appl. Physiol
Eng, A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response, Cancer Immunol. Immunother
Engblom, Microsomal prostaglandin E synthase-1 is the central switch during immuneinduced pyresis, Nature Neurosci
Engstrom, Lipopolysaccharide-induced fever depends on prostaglandin E2 production specifically in brain endothelial cells, Endocrinology
Ensor, Crawford, Hasday, Warming macrophages to febrile range destabilizes tumor necrosis factor-α mRNA without inducing heat shock, Am. J. Physiol
Ensor, Differential effects of hyperthermia on macrophage interleukin-6 and tumor necrosis factor-α expression, Am. J. Physiol
Evans, Bain, Wang, Fever-range hyperthermia stimulates α4β7 integrin-dependent lymphocyte-endothelial adhesion, Int. J. Hyperthermia
Evans, Dynamic association of L-selectin with the lymphocyte cytoskeletal matrix, J. Immunol
Evans, Fever-range hyperthermia dynamically regulates lymphocyte delivery to high endothelial venules, Blood
Facciponte, Wang, Subjeck, Hsp110 and Grp170, members of the Hsp70 superfamily, bind to scavenger receptor-A and scavenger receptor expressed by endothelial cells-I, Eur. J. Immunol
Fairchild, Viscardi, Hester, Singh, Hasday, Effects of hypothermia and hyperthermia on cytokine production by cultured human mononuclear phagocytes from adults and newborns, J. Interferon Cytokine Res
Fisher, Appenheimer, Evans, The two faces of IL-6 in the tumor microenvironment, Semin. Immunol
Fisher, IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells, J. Clin. Invest
Fiuza, Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells, Blood
Furuyashiki, Narumiya, Stress responses: the contribution of prostaglandin E 2 and its receptors, Nature Rev. Endocrinol
Girard, Moussion, Forster, Hevs, lymphatics and homeostatic immune cell trafficking in lymph nodes, Nature Rev. Immunol
Glaser, Kiecolt-Glaser, Stress-induced immune dysfunction: implications for health, Nature Rev. Immunol
Gothard, Ruffner, Woodward, Park-Sarge, Sarge, Lowered temperature set point for activation of the cellular stress response in T-lymphocytes, J. Biol. Chem
Griffith, Sokol, Luster, Chemokines and chemokine receptors: positioning cells for host defense and immunity, Annu. Rev. Immunol
Grivennikov, Greten, Karin, Immunity, inflammation, and cancer, Cell
Grupp, Chimeric antigen receptor-modified T cells for acute lymphoid leukemia, N. Engl. J. Med
Guo, Intratumoral injection of dendritic cells in combination with local hyperthermia induces systemic antitumor effect in patients with advanced melanoma, Int. J. Cancer
Gupta, Toll-like receptor agonists and febrile range hyperthermia synergize to induce heat shock protein 70 expression and extracellular release, J. Biol. Chem
Haemmerich, Laeseke, Thermal tumour ablation: devices, clinical applications and future directions, Int. J. Hyperthermia
Hagiwara, Iwasaka, Matsumoto, Noguchi, Changes in cell culture temperature alter release of inflammatory mediators in murine macrophagic RAW264.7 cells, Inflamm. Res
Hamzic, Interleukin-6 primarily produced by non-hematopoietic cells mediates the lipopolysaccharide-induced febrile response
Hanada, Central control of fever and female body temperature by RANKL/RANK, Nature
Hasday, Fairchild, Shanholtz, The role of fever in the infected host, Microbes Infect
Hasday, Febrile-range hyperthermia augments pulmonary neutrophil recruitment and amplifies pulmonary oxygen toxicity, Am. J. Pathol
Hasday, Thompson, Singh, Fever, immunity, and molecular adaptations, Compr. Physiol
Hashizume, Mihara, The roles of interleukin-6 in the pathogenesis of rheumatoid arthritis, Arthritis
Hatzfeld-Charbonnier, Influence of heat stress on human monocyte-derived dendritic cell functions with immunotherapeutic potential for antitumor vaccines, J. Leukoc. Biol
House, Effects of heat shock, stannous chloride, and gallium nitrate on the rat inflammatory response, Cell Stress Chaperones
Inouye, Heat shock transcription factor 1 opens chromatin structure of interleukin-6 promoter to facilitate binding of an activator or a repressor, J. Biol. Chem
Issels, Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft-tissue sarcoma: a randomised phase 3 multicentre study, Lancet Oncol
Ivanov, Romanovsky, Prostaglandin E 2 as a mediator of fever: synthesis and catabolism, Front. Biosci
Jiang, Exposure to febrile temperature upregulates expression of pyrogenic cytokines in endotoxin-challenged mice, Am. J. Physiol
Jiang, Febrile core temperature is essential for optimal host defense in bacterial peritonitis, Infect. Immun
Jones, References 209-211 demonstrate that thermal therapy has a clinical benefit when used in an adjuvant setting, J. Clin. Oncol
Jostock, Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses, Eur. J. Biochem
Kappel, Stadeager, Tvede, Galbo, Pedersen, Effects of in vivo hyperthermia on natural killer cell activity, in vitro proliferative responses and blood mononuclear cell subpopulations, Clin. Exp. Immunol
Karp, Murray, Non-canonical alternatives: what a macrophage is 4, J. Exp. Med
Katakai, Hara, Sugai, Gonda, Shimizu, Lymph node fibroblastic reticular cells construct the stromal reticulum via contact with lymphocytes, J. Exp. Med
Kluger, Phylogeny of fever, Fed. Proc
Knippertz, Mild hyperthermia enhances human monocyte-derived dendritic cell functions and offers potential for applications in vaccination strategies, Int. J. Hyperthermia
Kokolus, Baseline tumor growth and immune control in laboratory mice are significantly influenced by subthermoneutral housing temperature, Proc. Natl Acad. Sci
Kokolus, Stressful presentations: mild cold stress in laboratory mice influences phenotype of dendritic cells in naive and tumor-bearing mice, Front. Immunol
Kong, OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis, Nature
Konsman, Vigues, Mackerlova, Bristow, Blomqvist, Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactivity: relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli, J. Comp. Neurol
Kozak, IL-6 and IL-1β in fever. Studies using cytokine-deficient (knockout) mice, Ann. NY Acad. Sci
Kraybill, A phase I study of fever-range whole body hyperthermia (FR-WBH) in patients with advanced solid tumours: correlation with mouse models, Int. J. Hyperthermia
Kurosawa, Kobune, Okuyama, Sugiura, Effects of antipyretics in rinderpest virus infection in rabbits, J. Infect. Dis
Launey, Nesseler, Malledant, Seguin, Clinical review: fever in septic ICU patients-friend or foe?, Crit. Care
Lazarus, EP3 prostaglandin receptors in the median preoptic nucleus are critical for fever responses, Nature Neurosci
Lee, Defining immunological impact and therapeutic benefit of mild heating in a murine model of arthritis, Physiol. Rev
Lee, Repasky, Opposing roles for heat and heat shock proteins in macrophage functions during inflammation: a function of cell activation state?, Front. Immunol
Lee, Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing, Nature Immunol
Lee, Zhong, Mace, Repasky, Elevation in body temperature to fever range enhances and prolongs subsequent responsiveness of macrophages to endotoxin challenge, PLoS ONE
Lefor, Hyperthermia increases intercellular adhesion molecule-1 expression and lymphocyte adhesion to endothelial cells, Surgery
Lehner, Heat shock proteins generate β-chemokines which function as innate adjuvants enhancing adaptive immunity, Eur. J. Immunol
Li, Goorha, Ballou, Blatteis, Intracerebroventricular interleukin-6, macrophage inflammatory protein-1β and IL-18: pyrogenic and PGE 2 -mediated?, Brain Res
Liu, Naturally occurring hypothermia is more advantageous than fever in severe forms of lipopolysaccharide-and Escherichia coli-induced systemic inflammation, Am. J. Physiol. Regul. Integr. Comp. Physiol
Lwoff, From protozoa to bacteria and viruses. Fifty years with microbes (André Lwoff), Annu. Rev. Microbiol
Mace, Differentiation of CD8 + T cells into effector cells is enhanced by physiological range hyperthermia, J. Leukoc. Biol
Mace, Zhong, Kokolus, Repasky, A role for the thermal microenvironment in co-stimulation requirements during T cell activation, Int. J. Hyperthermia
Mackowiak, Fever: blessing or curse? A unifying hypothesis, Ann. Intern. Med
Malhotra, Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks, Nature Immunol
Manzella, Roberts, Human macrophage and lymphocyte responses to mitogen stimulation after exposure to influenza virus, ascorbic acid, and hyperthermia, J. Immunol
Marubayashi, HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans, J. Clin. Invest
Matsumura, Brain endothelial cells express cyclooxygenase-2 during lipopolysaccharide-induced fever: light and electron microscopic immunocytochemical studies, J. Neurosci
Mikucki, Preconditioning thermal therapy: flipping the switch on IL-6 for anti-tumour immunity, Int. J. Hyperthermia
Morrison, Madden, Tupone, Central control of brown adipose tissue thermogenesis, Front. Endocrinol
Mukhopadhaya, Localized hyperthermia combined with intratumoral dendritic cells induces systemic antitumor immunity, Cancer Res
Multhoff, Botzler, Wiesnet, Eissner, Issels, CD3large granular lymphocytes recognize a heat-inducible immunogenic determinant associated with the 72-kD heat shock protein on human sarcoma cells, Blood
Multhoff, Heat shock protein 70 (Hsp70): membrane location, export and immunological relevance, Methods
Muralidharan, Mandrekar, Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation, J. Leukoc. Biol
Nakai, Hayano, Furuta, Noda, Suzuki, Control of lymphocyte egress from lymph nodes through β 2 -adrenergic receptors, J. Exp. Med
Nakamura, Morrison, A thermosensory pathway that controls body temperature, Nature Neurosci
Neckers, Workman, Hsp90 molecular chaperone inhibitors: are we there yet?, Clin. Cancer Res
Nguyen, Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis, Nature
Nilsberth, Hamzic, Norell, Blomqvist, Peripheral lipopolysaccharide administration induces cytokine mRNA expression in the viscera and brain of fever-refractory mice lacking microsomal prostaglandin E synthase-1, J. Neuroendocrinol
Nilsberth, The role of interleukin-6 in lipopolysaccharide-induced fever by mechanisms independent of prostaglandin E 2, Endocrinology
Noessner, Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells, J. Immunol
O'neill, Golenbock, Bowie, The history of Toll-like receptors -redefining innate immunity, Nature Rev. Immunol
Osawa, Muschel, Studies relating to the serum resistance of certain Gram-negative bacteria, J. Exp. Med
Ostberg, Dayanc, Yuan, Oflazoglu, Repasky, Enhancement of natural killer (NK) cell cytotoxicity by fever-range thermal stress is dependent on NKG2D function and is associated with plasma membrane NKG2D clustering and increased expression of MICA on target cells, J. Leukoc. Biol
Ostberg, Ertel, Lanphere, An important role for granulocytes in the thermal regulation of colon tumor growth, Immunol. Invest
Ostberg, Gellin, Patel, Repasky, Regulatory potential of fever-range whole body hyperthermia on Langerhans cells and lymphocytes in an antigen-dependent cellular immune response, J. Immunol
Ostberg, Kaplan, Repasky, Induction of stress proteins in a panel of mouse tissues by fever-range whole body hyperthermia, Int. J. Hyperthermia
Ostberg, Repasky, Comparison of the effects of two different whole body hyperthermia protocols on the distribution of murine leukocyte populations, Int. J. Hyperthermia
Ostberg, Taylor, Baumann, Repasky, Regulatory effects of fever-range whole-body hyperthermia on the LPS-induced acute inflammatory response, J. Leukoc. Biol
Pabst, Binns, Heterogeneity of lymphocyte homing physiology: several mechanisms operate in the control of migration to lymphoid and nonlymphoid organs in vivo, Immunol. Rev
Padgett, Glaser, How stress influences the immune response, Trends Immunol
Palucka, Banchereau, Cancer immunotherapy via dendritic cells, Nature Rev. Cancer
Panjwani, Popova, Srivastava, Heat shock proteins gp96 and hsp70 activate the release of nitric oxide by APCs, J. Immunol
Patapoutian, Peier, Story, Viswanath, Delling et al., ThermoTRP channels and beyond: mechanisms of temperature sensation, Nature Rev. Neurosci
Peng, Monocyte-derived DC primed with TLR agonists secrete IL-12p70 in a CD40-dependent manner under hyperthermic conditions, J. Immunother
Picker, Butcher, Physiological and molecular mechanisms of lymphocyte homing, Annu. Rev. Immunol
Pockley, Calderwood, Santoro, Prokaryotic and Eukaryotic Heat Shock Proteins in Infectious Disease
Polderman, Induced hypothermia and fever control for prevention and treatment of neurological injuries, Lancet
Postic, Deangelis, Breinig, Monto, Effect of temperature on the induction of interferons by endotoxin and virus, J. Bacteriol
Pritchard, Li, Repasky, Nitric oxide production is regulated by fever-range thermal stimulation of murine macrophages, J. Leukoc. Biol
Repasky, Evans, Dewhirst, Temperature matters! And why it should matter to tumor immunologists, Cancer Immunol. Res
Restifo, Dudley, Rosenberg, Adoptive immunotherapy for cancer: harnessing the T cell response, Nature Rev. Immunol
Reynolds, Casterlin, Covert, (lizards and fish) develop fever through behavioural changes and that fever is associated with a survival benefit, Nature
Rice, Febrile-range hyperthermia augments neutrophil accumulation and enhances lung injury in experimental gram-negative bacterial pneumonia, J. Immunol
Ringheim, Burgher, Heroux, Interleukin-6 mRNA expression by cortical neurons in culture: evidence for neuronal sources of interleukin-6 production in the brain, J. Neuroimmunol
Roberts, Jr, Steigbigel, Hyperthermia and human leukocyte functions: effects on response of lymphocytes to mitogen and antigen and bactericidal capacity of monocytes and neutrophils, Infect. Immun
Romanovsky, Shido, Sakurada, Sugimoto, Nagasaka, Endotoxin shock: thermoregulatory mechanisms, Am. J. Physiol
Romanovsky, Thermoregulation: some concepts have changed. Functional architecture of the thermoregulatory system, Am. J. Physiol. Regul. Integr. Comp. Physiol
Rossi, Coccia, Trotta, Angelini, Santoro, STAT3 and MAPK signaling maintain overexpression of heat shock proteins 90α and β in multiple myeloma cells, which critically contribute to tumor-cell survival, PLoS ONE
Roth, Blatteis, Mechanisms of fever production and lysis: lessons from experimental LPS fever, Compr. Physiol
Rummel, Sachot, Poole, Luheshi, Circulating interleukin-6 induces fever through a STAT3-linked activation of COX-2 in the brain, Am. J. Physiol. Regul. Integr. Comp. Physiol
Ryan, Levy, Clinical review: fever in intensive care unit patients, Crit. Care
Saper, Romanovsky, Scammell, Neural circuitry engaged by prostaglandins during the sickness syndrome, Nature Neurosci
Sato, Involvement of heat-shock protein 90 in the interleukin-6-mediated signaling pathway through STAT3, Biochem. Biophys. Res. Commun
Sawada, Suzumura, Marunouchi, TNFα induces IL-6 production by astrocytes but not by microglia, Brain Res
Schmitt, Gehrmann, Brunet, Multhoff, Garrido, Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy, J. Leukoc. Biol
Schulman, The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study, Surg. Infect. (Larchmt)
Schumann, Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells, Immunity
Schurpf, Springer, Regulation of integrin affinity on cell surfaces, EMBO J
Sen, Mild elevation of body temperature reduces tumor interstitial fluid pressure and hypoxia and enhances efficacy of radiotherapy in murine tumor models, Cancer Res
Shah, Cytokine and adhesion molecule expression in primary human endothelial cells stimulated with fever-range hyperthermia, Int. J. Hyperthermia
Shang, Tomasi, The heat shock protein 90-CDC37 chaperone complex is required for signaling by types I and II interferons, J. Biol. Chem
Shen, Hornback, Shidnia, Shupe, Brahmi, Whole-body hyperthermia decreases lung metastases in lung tumor-bearing mice, possibly via a mechanism involving natural killer cells, J. Clin. Immunol
Shi, Hyperthermia enhances CTL crosspriming, J. Immunol
Simone-Finstrom, Foo, Tarpy, Starks, Impact of food availability, pathogen exposure, and genetic diversity on thermoregulation in honey bees (Apis mellifera), J. Insect Behav
Singh, He, Calderwood, Hasday, A high affinity HSF-1 binding site in the 5ʹ-untranslated region of the murine tumor necrosis factor-α gene is a transcriptional repressor, J. Biol. Chem
Singh, Heat shock co-activates interleukin-8 transcription, Am. J. Respir. Cell Mol. Biol
Slota, Shi, Chen, Bevans, Weng, Norepinephrine preferentially modulates memory CD8 T cell function inducing inflammatory cytokine production and reducing proliferation in response to activation, Brain Behav. Immun
Smith, Knowlton, Agarwal, Human lymphocyte responses are enhanced by culture at 40 °C, J. Immunol
Snyder, Guthrie, Evans, Zuckerman, Transcriptional inhibition of endotoxin-induced monokine synthesis following heat shock in murine peritoneal macrophages, J. Leukoc. Biol
Soehnlein, Lindbom, Phagocyte partnership during the onset and resolution of inflammation, Nature Rev. Immunol
Song, Park, Lee, Griffin, Implications of increased tumor blood flow and oxygenation caused by mild temperature hyperthermia in tumor treatment, Int. J. Hyperthermia
Steiner, Chakravarty, Rudaya, Herkenham, Romanovsky, Bacterial lipopolysaccharide fever is initiated via Toll-like receptor 4 on hematopoietic cells, Blood
Steinman, Nuanced roles of cytokines in three major human brain disorders, J. Clin. Invest
Sundgren-Andersson, Ostlund, Bartfai, IL-6 is essential in TNF-α-induced fever, Am. J. Physiol
Taipale, Jarosz, Lindquist, HSP90 at the hub of protein homeostasis: emerging mechanistic insights, Nature Rev. Mol. Cell Biol
Takada, Granulocyte-colony stimulating factor enhances anti-tumour effect of hyperthermia, Int. J. Hyperthermia
Tal, DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic endothelium and intralymphatic crawling, J. Exp. Med
Teachey, Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokinedirected therapy, Blood
Trepel, Mollapour, Giaccone, Neckers, Targeting the dynamic HSP90 complex in cancer, Nature Rev. Cancer
Tulapurkar, Asiegbu, Singh, Hasday, Hyperthermia in the febrile range induces HSP72 expression proportional to exposure temperature but not to HSF-1 DNA-binding activity in human lung epithelial A549 cells, Cell Stress Chaperones
Tulapurkar, Febrile-range hyperthermia modifies endothelial and neutrophilic functions to promote extravasation, Am. J. Respir. Cell. Mol. Biol
Turnbull, Prehar, Kennedy, Little, Hopkins, Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice, Endocrinology
Ulvmar, The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes, Nature Immunol
Vallieres, Rivest, Regulation of the genes encoding interleukin-6, its receptor, and gp130 in the rat brain in response to the immune activator lipopolysaccharide and the proinflammatory cytokine interleukin-1β, J. Neurochem
Van Bruggen, Robertson, Papadimitriou, The effect of mild hyperthermia on the morphology and function of murine resident peritoneal macrophages, Exp. Mol. Pathol
Vardam, Regulation of a lymphocyteendothelial-IL-6 trans-signaling axis by fever-range thermal stress: hot spot of immune surveillance, Cytokine
Vaughn, Bernheim, Kluger, Fever in the lizard Dipsosaurus dorsalis, Nature
Vega, Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages, J. Immunol
Von Andrian, Intravital microscopy of the peripheral lymph node microcirculation in mice, Microcirculation
Von Andrian, Mempel, Homing and cellular traffic in lymph nodes, Nature Rev. Immunol
Wang, Fever-range hyperthermia enhances L-selectin-dependent adhesion of lymphocytes to vascular endothelium, J. Immunol
Weber, Interstitial dendritic cell guidance by haptotactic chemokine gradients, Science
Weigert, Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition, J. Exp. Med
Wessalowski, Regional deep hyperthermia for salvage treatment of children and adolescents with refractory or recurrent non-testicular malignant germ-cell tumours: an open-label, non-randomised, single-institution, phase 2 study, Lancet Oncol
Whitesell, Lindquist, HSP90 and the chaperoning of cancer, Nature Rev. Cancer
Wolchok, Chan, Cancer: antitumour immunity gets a boost, Nature
Woodroofe, Detection of interleukin-1 and interleukin-6 in adult rat brain, following mechanical injury, by in vivo microdialysis: evidence of a role for microglia in cytokine production, J. Neuroimmunol
Xu, Fever-range whole body hyperthermia increases the number of perfused tumor blood vessels and therapeutic efficacy of liposomally encapsulated doxorubicin, Int. J. Hyperthermia
Yamagata, Coexpression of microsomal-type prostaglandin E synthase with cyclooxygenase-2 in brain endothelial cells of rats during endotoxininduced fever, J. Neurosci
Yan, Fever range temperature promotes TLR4 expression and signaling in dendritic cells, Life Sci
Yarwood, Heat of respiration of injured and diseased leaves, Phytopathology
Yenari, Antiapoptotic and antiinflammatory mechanisms of heat-shock protein protection, Ann. NY Acad. Sci
Yu, Pardoll, Jove, STATs in cancer inflammation and immunity: a leading role for STAT3, Nature Rev. Cancer
Zanker, Lange, Whole body hyperthermia and natural killer cell activity, Lancet
Zhu, Regulation of thermogenesis in plants: the interaction of alternative oxidase and plant uncoupling mitochondrial protein, J. Integr. Plant Biol
Zou, Guo, Guettouche, Smith, Voellmy, Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1, Cell
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