The Adaptive Value of Fever

Kluger, Matthew J.; Kozak, Wiesław; Conn, Carole A.; Leon, Lisa R.; Soszyński, Dariusz

doi:10.1016/s0891-5520(05)70282-8

Cited by 251 publications

(205 citation statements)

References 72 publications

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“…An elevation of the body temperature is part of the systemic inflammatory response to infection or tissue damage (15) and also to birth in the human newborn (16) and is believed to be a potent host defence (17).…”

Section: Discussionmentioning

confidence: 99%

Erythema Toxicum Neonatorum Is an Innate Immune Response to Commensal Microbes Penetrated into the Skin of the Newborn Infant

et al. 2005

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Erythema toxicum neonatorum is a common rash of unknown etiology affecting healthy newborn infants. In this study, we postulated that the rash reflects a response to microbial colonization of the skin at birth, and that the hair follicle constitutes an "easily opened door" for microbes into the skin of the newborn. We collected microbial cultures from the skin of 69 healthy, 1-d-old infants with and without erythema toxicum to identify the colonizing flora and correlate culture results with clinical findings. We also analyzed biopsies from lesions of erythema toxicum with scanning and transmission electron microscopy in the search for microbes. Finally, each infant's body temperature was measured as a sign of acute phase response. We found that 84% of 1-d-old healthy infants, with and without erythema toxicum were colonized with coagulase-negative staphylococci. In all lesions of erythema toxicum, TEM identified cocci-like bacteria localized in the hair follicle epithelium and into recruited immune cells surrounding the hair follicle; morphology and dimension supported their identification as belonging to the genus Staphylococcus. SEM revealed 10 times more hair structures per skin surface unit in newborns compared with adults. Infants with erythema toxicum also had higher body temperature. In erythema toxicum, commensal microbes gain entry into the skin tissue, most probably through the hair canal. This triggers the local immune system and a systemic acute phase response, including an increase in body temperature. We speculate that early microbial exposure to the newborn may be important for the maturation of the immune system. (Pediatr Res 58: 613-616, 2005) Abbreviations CoNS, coagulase-negative Staphylococcus SEM, scanning electron microscopy TEM, transmission electron microscopy Erythema toxicum neonatorum is an acute, self-limiting skin manifestation that develops in 50 -70% of all healthy newborn infants, particularly those born at term (Fig. 1) (1). It starts soon after birth and disappears spontaneously within a few weeks without leaving sequelae. Infants with it have papulopustules on an intense erythematous base. The presence of the rash is often a matter of concern for parents with affected newborns and may be misinterpreted by healthcare professionals, leading to unnecessary investigations and inappropriate therapies. Its etiology has been attributed to hematological, toxic, and allergic factors but still remains to be determined (2-4). Histology shows a dense inflammatory infiltrate around hair follicles, composed mostly of eosinophils, but also containing neutrophils, macrophages, and dendritic cells, as well as an up-regulation of various inflammatory mediators such as IL-1, IL-8, eotaxin, psoriasin, and nitric oxide synthases 1-3 (5-8). The rash has been suggested to reflect a response to the presence, for the first time, of microbes on the skin of the newborn infant (8).In this study, we postulated that the skin appendages, especially the hair follicles, might act as an entry port for microbes,...

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Section: Discussionmentioning

confidence: 99%

Erythema Toxicum Neonatorum Is an Innate Immune Response to Commensal Microbes Penetrated into the Skin of the Newborn Infant

et al. 2005

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“…At these temperatures, decreased toad mortality is more likely due to greater effectiveness of the amphibian immune response to Bd (sensu Matutte et al 2000) than the reduced growth rate of Bd. In severely infected toads post-Exposure 2, this increase in resistance had a behavioral component as toads shifted their resting position towards heat strips, suggesting behavioral fever (Kluger 1978) to combat Bd infection. Providing moderate heat also decreased secondary effects of Bd infection.…”

mentioning

confidence: 99%

Temperature, hydric environment, and prior pathogen exposure alter the experimental severity of chytridiomycosis in boreal toads

Murphy¹,

St‐Hilaire²,

Corn³

2011

Dis. Aquat. Org.

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Prevalence of the pathogen Batrachochytrium dendrobatidis (Bd), implicated in amphibian population declines worldwide, is associated with habitat moisture and temperature, but few studies have varied these factors and measured the response to infection in amphibian hosts. We evaluated how varying humidity, contact with water, and temperature affected the manifestation of chytridiomycosis in boreal toads Anaxyrus (Bufo) boreas boreas and how prior exposure to Bd affects the likelihood of survival after re-exposure, such as may occur seasonally in long-lived species. Humidity did not affect survival or the degree of Bd infection, but a longer time in contact with water increased the likelihood of mortality. After exposure to ~106 Bd zoospores, all toads in continuous contact with water died within 30 d. Moreover, Bd-exposed toads that were disease-free after 64 d under dry conditions, developed lethal chytridiomycosis within 70 d of transfer to wet conditions. Toads in unheated aquaria (mean = 15°C) survived less than 48 d, while those in moderately heated aquaria (mean = 18°C) survived 115 d post-exposure and exhibited behavioral fever, selecting warmer sites across a temperature gradient. We also found benefits of prior Bd infection: previously exposed toads survived 3 times longer than Bd-naïve toads after re-exposure to 10 6 zoospores (89 vs. 30 d), but only when dry microenvironments were available. This study illustrates how the outcome of Bd infection in boreal toads is environmentally dependent: when continuously wet, high reinfection rates may overwhelm defenses, but periodic drying, moderate warming, and previous infection may allow infected toads to extend their survival.KEY WORDS: Boreal toads · Disease severity · Chytridiomycosis · Temperature · Moisture · Acquired immunity Resale or republication not permitted without written consent of the publisherDis Aquat Org 95: 31-42, 2011 32 lethal chytridiomycosis, however, depends not only on Bd, but on the host's immune response. Resistance to Bd has been linked to antimicrobial skin peptides and other hydrophobic molecules (Woodhams et al. 2007, Rollins-Smith et al. 2009) and cutaneous bacteria (Harris et al. 2006), both of which may change in effectiveness depending on body temperature and hydric environment (Matutte et al. 2000, Rollins-Smith et al. 2002.Although the effects of varying temperature on chytridiomycosis have been studied experimentally, the outcomes in vivo have not always been consistent with the temperature optima of Bd in pure culture. For example, Carey et al. (2006) found no difference in survival time in infected boreal toads Anaxyrus boreas boreas housed at 12 and 23°C, although 12°C is well below the optimal growth range of Bd. Likewise, 2 studies have found that moderate changes in temperature within the optimal growth range of Bd (from 17 to 22-23°C) increased survival in exposed amphibians (Andre et al. 2008, Bustamante et al. 2010. Amphibians often modify their body temperature behaviorally, including in response t...

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“…F ever is generally regarded as a protective response to infection (1). Retrospective clinical studies demonstrate an association between the presence of fever and reduced length of viral illnesses (2)(3)(4)(5) or improved survival in bacterial infections (6 -10).…”

mentioning

confidence: 99%

Febrile-Range Hyperthermia Augments Neutrophil Accumulation and Enhances Lung Injury in Experimental Gram-Negative Bacterial Pneumonia

Rice

Martin

et al. 2005

The Journal of Immunology

101

109

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We previously demonstrated that exposure to febrile-range hyperthermia (FRH) accelerates pathogen clearance and increases survival in murine experimental Klebsiella pneumoniae peritonitis. However, FRH accelerates lethal lung injury in a mouse model of pulmonary oxygen toxicity, suggesting that the lung may be particularly susceptible to injurious effects of FRH. In the present study, we tested the hypothesis that, in contrast with the salutary effect of FRH in Gram-negative peritonitis, FRH would be detrimental in multilobar Gram-negative pneumonia. Using a conscious, temperature-clamped mouse model and intratracheal inoculation with K. pneumoniae Caroli strain, we showed that FRH tended to reduce survival despite reducing the 3 day-postinoculation pulmonary pathogen burden by 400-fold. We showed that antibiotic treatment rescued the euthermic mice, but did not reduce lethality in the FRH mice. Using an intratracheal bacterial endotoxin LPS challenge model, we found that the reduced survival in FRH-treated mice was accompanied by increased pulmonary vascular endothelial injury, enhanced pulmonary accumulation of neutrophils, increased levels of IL-1β, MIP-2/CXCL213, GM-CSF, and KC/CXCL1 in the bronchoalveolar lavage fluid, and bronchiolar epithelial necrosis. These results suggest that FRH enhances innate host defense against infection, in part, by augmenting polymorphonuclear cell delivery to the site of infection. The ultimate effect of FRH is determined by the balance between accelerated pathogen clearance and collateral tissue injury, which is determined, in part, by the site of infection.

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The Adaptive Value of Fever

Cited by 251 publications

References 72 publications

Erythema Toxicum Neonatorum Is an Innate Immune Response to Commensal Microbes Penetrated into the Skin of the Newborn Infant

Erythema Toxicum Neonatorum Is an Innate Immune Response to Commensal Microbes Penetrated into the Skin of the Newborn Infant

Temperature, hydric environment, and prior pathogen exposure alter the experimental severity of chytridiomycosis in boreal toads

Febrile-Range Hyperthermia Augments Neutrophil Accumulation and Enhances Lung Injury in Experimental Gram-Negative Bacterial Pneumonia

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