Sex differences in the pro-inflammatory cytokine response to endotoxin unfold <i>in vivo</i> but not <i>ex vivo</i> in healthy humans

Wegner, Alexander; Benson, Sven; Rebernik, Laura; Spreitzer, Ingo; Jäger, Markus; Schedlowski, Manfred; Elsenbruch, Sigrid; Engler, Harald

doi:10.1177/1753425917707026

Cited by 55 publications

(55 citation statements)

References 40 publications

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“…Interestingly, such as with depression [43], there is some evidence for sex differences in the inflammatory and behavioral responses to experimental endotoxemia [44], but so far the findings are inconsistent. Some studies found a heighted pro-inflammatory response and more pronounced mood disturbances after LPS administration in women compared to men, while others did not [45][46][47][48][49][50]. It is possible that this heterogeneity is related to the hormonal status of the female volunteers, but this needs to be confirmed in future studies.…”

Section: Endotoxin-induced Inflammation: Effects On Mood and Behaviormentioning

confidence: 99%

Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression

et al. 2020

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Depression is one of the global leading causes of disability, but treatments remain limited and classical antidepressants were found to be ineffective in a substantial proportion of patients. Thus, novel effective therapies for the treatment of depression are urgently needed. Given the emerging role of inflammation in the etiology and pathophysiology of affective disorders, we herein illustrate how experimental endotoxemia, a translational model of systemic inflammation, could be used as a tool to develop and test new therapeutic options against depression. Our concept is based on the striking overlap of inflammatory, neural, and affective characteristics in patients with inflammation-associated depression and in endotoxin-challenged healthy subjects. Experimental administration of endotoxin in healthy volunteers is safe, well-tolerated, and without known longterm health risks. It offers a highly standardized translational approach to characterize potential targets of therapies against inflammation-associated depression, as well as to identify characteristics of patients that would benefit from these interventions, and, therefore, could contribute to improve personalization of treatment and to increase the overall rate of responders.

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Section: Endotoxin-induced Inflammation: Effects On Mood and Behaviormentioning

confidence: 99%

Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression

et al. 2020

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“…In contrast to other studies, the authors found no significant differences when looking at sex and inflammatory markers in relation to adipose tissue. In another study aimed at elucidating mechanisms responsible for differences in inflammatory responses across sexes, Wegner et al found that proinflammatory responses to endotoxin in women were greater compared to Sex Differences in Obesity-Induced Inflammation DOI: http://dx.doi.org/10.5772/intechopen.84941 men, with significantly higher increases in plasma TNF-alpha and IL-6 [32]. Interestingly, increases in circulating plasma cortisol levels were also found to be significantly elevated in women as compared to men, which could play a role in the heightened response.…”

Section: Gender-specific Differences In Aging Due To Inflammationmentioning

confidence: 99%

Sex Differences in Obesity-Induced Inflammation

Terrazas¹,

Brashear²,

Escoto³

et al. 2020

Translational Studies on Inflammation

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Obesity is defined as a BMI greater than 25 kg/m 2. Once thought to simply be a nutritional disorder, obesity has become a major health concern characterized by a state of constant low-grade inflammation caused by chronic adiposity. This state of inflammation is characterized by circulating inflammatory mediators, such as IL-6, leptin, and TNF-α, as well as varying levels of glucose-regulating hormones produced by obese adipose tissue. When left untreated, obesity can lead to a number of diseases including, but not limited to, cardiovascular disease, metabolic syndrome, neurodegeneration, type II diabetes mellitus, chronic kidney disease, and infertility. The distribution of adiposity differs in men and women, and these differences, along with the differences in sex hormones and sex hormone levels, can exacerbate or attenuate the course of disease pathology. Obesity can also be exacerbated by stress, which can worsen disease pathogenesis. In this review, we will explore how obesity affects inflammation and disease and how sex can affect the course of these diseases.

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“…Another limitation was the use of a mixed-gender population for the ex vivo model in comparison to an all-male population in vivo, which might influence the differences observed in immune response between the two models. Wegner et al observed a higher pro-inflammatory cytokine response to LPS in females compared to males, which was significant only in vivo but not ex vivo 36 . Nonetheless, we performed a preliminary analysis on the healthy volunteers population (n = 180) in the REALISM project 37 and so far we didn't observe a significant gender-related difference for the transcriptomic markers included in the IPP tool (unpublished data).…”

Section: Discussionmentioning

confidence: 93%

Comparison of host immune responses to LPS in human using an immune profiling panel, in vivo endotoxemia versus ex vivo stimulation

Tawfik

Lankelma

Vachot

et al. 2020

Sci Rep

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Patients that suffer from sepsis exhibit an early hyper-inflammatory immune response which can lead to organ failure and death. In our study, we assessed the immune modulation in the human in vivo endotoxemia model and compared it to ex vivo LPS stimulation using 38 transcriptomic markers. Blood was collected before and after 4 hours of LPS challenge and tested with the Immune Profiling Panel (IPP) using the FilmArray system. The use of IPP showed that markers from the innate immunity dominated the response to LpS in vivo, mainly markers related to monocytes and neutrophils. Comparing the two models, in vivo and ex vivo, revealed that most of the markers were modulated in a similar pattern (68%). Some cytokine markers such as TNF, IFN-γ and IL-1β were under-expressed ex vivo compared to in vivo. T-cell markers were either unchanged or up-modulated ex vivo, compared to a down-modulation in vivo. Interestingly, markers related to neutrophils were expressed in opposite directions, which might be due to the presence of cell recruitment and feedback loops in vivo. the ipp tool was able to capture the early immune response in both the human in vivo endotoxemia model, a translational model mimicking the immune response observed in septic patients.

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Sex differences in the pro-inflammatory cytokine response to endotoxin unfold in vivo but not ex vivo in healthy humans

Cited by 55 publications

References 40 publications

Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression

Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression

Sex Differences in Obesity-Induced Inflammation

Comparison of host immune responses to LPS in human using an immune profiling panel, in vivo endotoxemia versus ex vivo stimulation

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