Age and sex differences in immune response following LPS treatment in mice

Cai, Kyle Chiman; Mil, Spencer van; Murray, E. Selkirk; Mallet, Jean‐François; Matar, Chantal; Ismail, Nafissa

doi:10.1016/j.bbi.2016.08.002

Cited by 107 publications

(90 citation statements)

References 63 publications

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“…Systemic LPS treatment causes an increase in plasma cytokine production, such as IL‐6, TNFα, IL‐1β, IFNγ, IL‐10, and IL‐12 (Cai et al, 2016; Correa et al, 2007; Erickson and Banks, 2011; Kim et al, 2007), and stress hormones, such as ACTH and corticosterone (Bison et al, 2009; Takao et al, 1997). ACTH functions as a potent inducer of synthesis and secretion of numerous cytokines such as IL‐1β, IL‐6, and TNFα (Anisman et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Taken together, the combination of increased peripheral corticosterone and TNFα of adult females gives rise to their earlier onset of sickness behaviour (i.e., 30 min) whereas the pubertal females show a delayed peak onset of sickness behaviour (i.e., 4 h). The sickness behaviour also relates to the delayed LPS‐induced hypothermia experienced by pubertal females compared to their adult counterparts (Cai et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Pubertal mice also display fewer body temperature fluctuations and sickness behaviour symptoms compared to their adult counterparts after LPS treatment. Furthermore, LPS treatment induces more pro‐inflammatory cytokines, like IL‐1β, IFNγ, and TNFα, in adult mice and more anti‐inflammatory cytokines, such as IL‐10, in pubertal mice ten hours following exposure (Cai et al, 2016). Therefore, there are important age and sex differences in the acute immune response to LPS exposure suggesting that pubertal mice may be hypo‐responsive to an immune challenge compared to their adult counterparts.…”

Section: Introductionmentioning

confidence: 99%

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Sex differences in the peripheral and central immune responses following lipopolysaccharide treatment in pubertal and adult CD‐1 mice

Sharma

Rooke

Kolmogorova

et al. 2018

Intl J of Devlp Neuroscience

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Puberty is a critical developmental period that is characterized by significant brain development. Exposure to stress during this time can alter brain functioning setting the stage for long-lasting behavioural outcomes. The objective of this study was to investigate age and sex differences in the peripheral and central immune responses, along with sickness behaviour, following immune stress. The results showed that LPS treatment increased serum cytokine levels and sickness symptoms in all mice. Pubertal males displayed increased IL-1β concentrations at 2 h and increased IL-6 concentrations at 8 h post-treatment whereas increased concentrations of TNFα, IL-10, IL-12, IL-1β, IFNγ, and IL-6 persisted at 8 and 24 h in adult females. Consistent with peripheral cytokines, pubertal males displayed greater IL-1β, TNFα, and IL-6 mRNA expression in the prefrontal cortex at 2 h, whereas adult males expressed more of the aforementioned cytokines at 8 h compared to saline controls. Adult males also displayed greater IL-1β mRNA expression compared to their female counterparts, and adult females displayed greater TNFα mRNA expression compared to their male counterparts. These results not only provide a better understanding of the age and sex differences in acute immune response, but also show important region- and time-specific differences in the response to an immune challenge, and that the peripheral immune response differs from the central response. This highlights the need to examine immune markers in both the periphery and the central nervous system for an accurate depiction of acute immune response following an immune challenge.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex differences in the peripheral and central immune responses following lipopolysaccharide treatment in pubertal and adult CD‐1 mice

Sharma

Rooke

Kolmogorova

et al. 2018

Intl J of Devlp Neuroscience

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“…Many studies suggest that there are complex interactions between sex steroids and the immune system, and that testosterone is an immune suppressor, whereas, estrogens are immune enhancers [48]. Thus, it is possible that females may have a more intense cellular and humoral immune response following LPS exposure and that they are more strongly affected by treatment than males [49]. In our study, however, we investigated only a subset of the potential measures to determine effects of LPS on physiology; therefore, it is possible that not all aspects of physiology are affected in the same manner.…”

Section: Discussionmentioning

confidence: 99%

“…Exposure to exogenous LPS increases cytokine levels in pubertal and adult mice as well. More specifically, pro-inflammatory cytokines are higher in adult mice than in pubertal mice, but pubertal mice administered LPS exhibit greater levels of anti-inflammatory cytokines than LPS-treated adult mice [49]. …”

Section: Discussionmentioning

confidence: 99%

Overcoming neonatal sickness: Sex-specific effects of sickness on physiology and social behavior

Sylvia

Demas

2017

Physiology & Behavior

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Early-life environmental stressors, including sickness, have the potential to disrupt development in ways that could severely impact fitness. Despite what is known about the effects of sickness on reproduction, the precise physiological mechanisms have not yet been determined. The goal of this study was to investigate the effects of a neonatal immune challenge on adult reproductive physiology and opposite-sex social behavior. Male and female Siberian hamster (Phodopus sungorus) pups were administered lipopolysaccharide ([LPS]; a cell wall component of gram-negative bacteria) or saline injections on postnatal days 3 and 5 and body mass, food intake, and measures of reproductive maturity were taken throughout development. In adulthood, hamsters were placed in staged mating pairs with reproductively mature individuals of the opposite sex, during which a series of behaviors were scored. We found that although males and females showed no change in food intake, body mass, or reproductive behaviors, LPS-treated females had abnormal estrous cycles and smaller ovaries. Females also showed increased investigation of and increased aggression towards males in a reproductive context. In contrast, LPS-treated males showed no change in any physiological measures, nor did they show any changes in behavior. The present findings demonstrate that females may be more robustly affected by neonatal sickness than males and that these effects could have potential impacts on reproductive success. Collectively, the results of this study can be used to expand upon what is already known about sickness and reproduction, specifically the importance of social behaviors involved in pre-copulation and information necessary to choose the appropriate mate.

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KCND2: A prognostic biomarker and regulator of immune function in gastric cancer

Zhou

Chen

et al. 2023

Cancer Medicine

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BackgroundGastric cancer is a highly heterogeneous disease, which makes it challenging to develop effective targeted therapies. Although the potassium voltage‐gated channel subfamily D (KCND) channels, particularly KCND2 (also known as Kv4.2), have found evidence of involvement in the occurrence and development of various cancers, there are still some limitations in our understanding of KCND2's roles in gastric cancer.MethodsWe analyzed the correlation between KCND2 expression and clinical features as well as immune infiltration using the Cancer Genome Atlas (TCGA) database. Functional assays of KCND2 were conducted using Cell counting Kit‐8 (CCK8), clone formation assay and cell cycle analysis. Additionally, immunofluorescence, flow cytometry and quantitative real‐time polymerase chain reaction (qRT‐PCR) techniques were used to investigate tumor proliferation and immune cell infiltration at different levels of KCND2 expression in vivo.ResultsKCND2 was markedly elevated in gastric cancer and its expression appeared to link to different grades, T stages, and N stages. In addition, KCND2 was an independent predictor of prognosis, and its elevated levels in TCGA database revealed a more unfavorable prognosis for patients with gastric cancer. KCND2 strengthened the viability at the cellular level by boosting the proliferation of gastric cancer cells and reducing their death rate. Additionally, it also highlights that KCND2 the abilities of proliferating of gastric cancer cells by stimulating NF‐κB both in cell and animal levels. In addition, the findings provided proof that in animal levels, KCND2 might regulate the immune system by associating with promoting M2 macrophages, which are known to play critical roles in cancer progression. Mechanistically, KCND2 was found to lead to the infiltration of M2 macrophages through activation of NF‐κB, ultimately promoting the advancement of gastric cancer.ConclusionOverall, these findings suggest that KCND2 is likely to be available as an underlying therapeutic target for gastric cancer.

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Age and sex differences in immune response following LPS treatment in mice

Cited by 107 publications

References 63 publications

Sex differences in the peripheral and central immune responses following lipopolysaccharide treatment in pubertal and adult CD‐1 mice

Sex differences in the peripheral and central immune responses following lipopolysaccharide treatment in pubertal and adult CD‐1 mice

Overcoming neonatal sickness: Sex-specific effects of sickness on physiology and social behavior

KCND2: A prognostic biomarker and regulator of immune function in gastric cancer

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