Neonatal bacterial infection alters fever to live and simulated infections in adulthood

Bilbo, Staci D.; Wieseler, Julie; Barrientos, Ruth M.; Tsang, Verne; Watkins, Linda R.; Maier, Steven F.

doi:10.1016/j.psyneuen.2009.07.014

Cited by 28 publications

(26 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Seven studies evaluated TLRs on microglia, by qPCR, immunohistochemistry, in situ hybridization, or flow cytometry: four evaluated TLR-2 expression [3, 21, 33, 34] and three TLR-4 expression [4, 35, 36]. Three studies described TLR-2 upregulation [3, 21, 33] and two TLR-4 upregulation [4, 36].…”

Section: Resultsmentioning

confidence: 99%

“…Interleukin 1 beta (IL-1β) protein levels or mRNA expression were determined in 16 studies [4–6, 8, 9, 21, 22, 30, 32, 35, 37, 39–43], at 24 different time points after challenge. At 13 time points microglial activation was present in combination with increased IL-1β protein levels or mRNA expression patterns, from 4 h to 1 week after LPS challenge ( n = 7), from 1 and 56 days after E. coli challenge ( n = 2), and from 4 h to 3 weeks after CFA challenge ( n = 4).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Systemic inflammation and microglial activation: systematic review of animal experiments

Hoogland

Houbolt

Westerloo

et al. 2015

J Neuroinflammation

734

548

View full text Add to dashboard Cite

BackgroundAnimal studies show that peripheral inflammatory stimuli may activate microglial cells in the brain implicating an important role for microglia in sepsis-associated delirium. We systematically reviewed animal experiments related to the effects of systemic inflammation on the microglial and inflammatory response in the brain.MethodsWe searched PubMed between January 1, 1950 and December 1, 2013 and Embase between January 1, 1988 and December 1, 2013 for animal studies on the influence of peripheral inflammatory stimuli on microglia and the brain. Identified studies were systematically scored on methodological quality. Two investigators extracted independently data on animal species, gender, age, and genetic background; number of animals; infectious stimulus; microglial cells; and other inflammatory parameters in the brain, including methods, time points after inoculation, and brain regions.ResultsFifty-one studies were identified of which the majority was performed in mice (n = 30) or in rats (n = 19). Lipopolysaccharide (LPS) (dose ranging between 0.33 and 200 mg/kg) was used as a peripheral infectious stimulus in 39 studies (76 %), and live or heat-killed pathogens were used in 12 studies (24 %). Information about animal characteristics such as species, strain, sex, age, and weight were defined in 41 studies (80 %), and complete methods of the disease model were described in 35 studies (68 %). Studies were also heterogeneous with respect to methods used to assess microglial activation; markers used mostly were the ionized calcium binding adaptor molecule-1 (Iba-1), cluster of differentiation 68 (CD68), and CD11b. After LPS challenge microglial activation was seen 6 h after challenge and remained present for at least 3 days. Live Escherichia coli resulted in microglial activation after 2 days, and heat-killed bacteria after 2 weeks. Concomitant with microglial response, inflammatory parameters in the brain were reviewed in 23 of 51 studies (45 %). Microglial activation was associated with an increase in Toll-like receptor (TLR-2 and TLR-4), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) messenger ribonucleic acid (mRNA) expression or protein levels.InterpretationAnimal experiments robustly showed that peripheral inflammatory stimuli cause microglial activation. We observed distinct differences in microglial activation between systemic stimulation with (supranatural doses) LPS and live or heat-killed bacteria.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Systemic inflammation and microglial activation: systematic review of animal experiments

Hoogland

Houbolt

Westerloo

et al. 2015

J Neuroinflammation

734

548

View full text Add to dashboard Cite

show abstract

“…With the use of a similar neonatal LPS administration, Walker et al (2006) observed a marked attenuation in febrile response in nLPS (P3-5) treated males exposed to an adult LPS challenge, but no changes in CORT level was observed. In contrast, Bilbo et al (2010) used n E. coli infection on P4 rats and found that adult febrile responses to LPS were largely unchanged. In addition, neonatally treated animals also exhibited an altered sensitization of the effects of nLPS to adult LPS challenge (Bilbo et al, 2010).…”

Section: Innate Immune Responsementioning

confidence: 95%

“…In contrast, Bilbo et al (2010) used n E. coli infection on P4 rats and found that adult febrile responses to LPS were largely unchanged. In addition, neonatally treated animals also exhibited an altered sensitization of the effects of nLPS to adult LPS challenge (Bilbo et al, 2010). Our group has carried out extensive investigations of the effects of nLPS administered at P14 on adult male neuroimmune responses; to summarize, we found that neonatally LPS treated animals exhibit significantly attenuated febrile response to adult LPS challenge due to amplified corticosteroid responses that suppress cytokine production (Ellis et al, 2005;Galic et al, 2009).…”

Section: Innate Immune Responsementioning

confidence: 95%

Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

Rana

Aavani

Pittman

2012

Hormones and Behavior

View full text Add to dashboard Cite

Humans are exposed to potentially harmful agents (bacteria, viruses, toxins) throughout our lifespan; the consequences of such exposure can alter central nervous system development. Exposure to immunogens during pregnancy increases the risk of developing neurological disorders such as schizophrenia and autism. Further, sex hormones, such as estrogen, have strong modulatory effects on immune function and have also been implicated in the development of neuropathologies (e.g., schizophrenia and depression). Similarly, animal studies have demonstrated that immunogen exposure in utero or during the neonatal period, at a time when the brain is undergoing maturation, can induce changes in learning and memory, as well as dopaminemediated behaviors in a sex-specific manner. Literature that covers the effects of immunogens on innate immune activation and ultimately the development of the adult brain and behavior is riddled with contradictory findings, and the addition of sex as a factor only adds to the complexity. This review provides evidence that innate immune activation during critical periods of development may have effects on the adult brain in a sex-specific manner. Issues regarding sex bias in research as well as variability in animal models of immune function are discussed.

show abstract

“…For instance, maternal transfer of hormones or other molecules to eggs can influence physiological, behavioral and immunological phenotypes in offspring (Saino et al, 2002;Groothuis et al, 2005;Grindstaff et al, 2006;Gasparini et al, 2009;Hasselquist and Nilsson, 2009). In addition, in several mammalian species, early life exposure to stressors and pathogens can program immune responses in later life (Galic et al, 2009;Bilbo et al, 2010). In contrast to these examples of plasticity in ovo and during early life, differential cytokine and febrile responses have been artificially selected between strains of chickens (Leshchinsky and Klasing, 2001), suggesting a potential genetic component to variation in the acute phase response.…”

Section: Evolved Versus Plastic Differences In the Acute Phase Responsementioning

confidence: 99%

Population differences in fever and sickness behaviors in a wild passerine: a role for cytokines

Adelman

Bentley

Wingfield

et al. 2010

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARYImmune responses benefit hosts by clearing pathogens, but they also incur physiological costs and tissue damage. While wild animals differ in how they balance these costs and benefits, the physiological mechanisms underlying such differential investment in immunity remain unknown. Uncovering these mechanisms is crucial to determining how and where selection acts to shape immunological defense. Among free-living song sparrows (Melospiza melodia) in western North America, sicknessinduced lethargy and fever are more pronounced in Southern California than in Washington and Alaska. We brought song sparrows from two populations (Southern California and Washington) into captivity to determine whether these differences persist in a common environment and what physiological signals facilitate such differences. As in free-living sparrows, captive California birds exhibited more pronounced fever and lethargy than Washington birds in response to lipopolysaccharide, a nonpathogenic antigen that mimics bacterial infection. After treatment, the two populations showed similar reductions in luteinizing hormone levels, food intake and body mass, although treated birds from California lost more breast muscle tissue than treated birds from Washington. Moreover, California birds displayed higher bioactivity of interleukin-6, a pro-inflammatory cytokine, and marginally higher levels of corticosterone, a steroid hormone involved in stress, metabolism and regulating inflammatory responses. Our results show that immunological differences between these populations cannot be explained by immediate environment alone and may reflect genetic, maternal or early-life effects. Additionally, they suggest that cytokines play a role in shaping immunological variation among wild vertebrates. Supplementary material available online at

show abstract

Neonatal bacterial infection alters fever to live and simulated infections in adulthood

Cited by 28 publications

References 59 publications

Systemic inflammation and microglial activation: systematic review of animal experiments

Systemic inflammation and microglial activation: systematic review of animal experiments

Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

Population differences in fever and sickness behaviors in a wild passerine: a role for cytokines

Contact Info

Product

Resources

About