Bedeutung der angeborenen Immunantwort in der Sepsis

Hörner, Christian; Bouchon, Axel; Bierhaus, Angelika; Nawroth, Peter P.; Martin, Eike; Hj, Bardenheuer; Weigand, Markus A.

doi:10.1007/s00101-003-0626-4

Cited by 11 publications

(4 citation statements)

References 217 publications

(137 reference statements)

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“…Other studies have found that binge drinking in human subjects, as well as binge-like exposure to EtOH in rodents, induces gut leakage that elevates the blood endotoxin concentration (15, 16), which leads to production of inflammatory molecules, as well as greater activity of neuroimmune signaling pathways (19, 20). As noted previously, binge-like exposure to high-dose, high-concentration EtOH can trigger a severe immune response that persists even after EtOH has been metabolized (Figures 1, 2) (57).…”

Section: Discussionmentioning

confidence: 57%

Binge-Like Exposure to Ethanol Enhances Morphine's Anti-nociception in B6 Mice

Chang

Huang

Han³

et al. 2019

Front. Psychiatry

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Elevation of the blood ethanol concentration (BEC) to > 80 mg/dL (17.4 mM) after binge drinking enhances inflammation in brain and neuroimmune signaling pathways. Morphine abuse is frequently linked to excessive drinking. Morphine exerts its actions mainly via the seven transmembrane G-protein-coupled mu opioid receptors (MORs). Opioid use disorders (OUDs) include combination of opioids with alcohol, leading to opioid overdose-related deaths. We hypothesized that binge drinking potentiates onset and progression of OUD. Using C57BL/6J (B6) mice, we first characterized time-dependent inflammatory gene expression change as molecular markers using qRT-PCR within 24 h after binge-like exposure to high-dose, high-concentration ethanol (EtOH). The mice were given one injection of EtOH (5 g/kg, 42% v/v, i.g.) and sacrificed at 2.5 h, 5 h, 7.5 h, or 24 h later. Inflammatory cytokines interleukin (IL)-1β, IL-6, and IL-18 were elevated in both the striatum (STr) and the nucleus accumbens (NAc) of the mice. We then investigated the expression profile of MOR in the STr at 2 min, 5 h, or 24 h after the first EtOH injection and at 24 h and 48 h after the third injection. This binge-like exposure to EtOH upregulated MOR expression in the STr and NAc, an effect that could enhance morphine's anti-nociception. Therefore, we examined the impact of binge-like exposure to EtOH on morphine's anti-nociception at the behavioral level. The mice were treated with or without 3-d binge-like exposure to EtOH, and the anti-nociceptive changes were evaluated using the hot-plate test 24 h after the final (3rd) EtOH injection with or without a cumulative subcutaneous dose (0, 0.1, 0.3, 1.0, and 3.0 mg/kg) of morphine at intervals of 30 min. The response curve of the mice given EtOH was shifted to the left, showing enhanced latency to response to morphine up to 3 mg/kg. Furthermore, co-treatment with the MOR antagonist naltrexone blocked morphine's anti-nociception in animals given either EtOH or saline. This confirms that MOR is involved in binge-like exposure to EtOH-induced changes in morphine's anti-nociception. Our results suggest that EtOH enhanced latency to analgesic response to morphine, and such effect might initiate the onset and progression of OUDs.

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Section: Discussionmentioning

confidence: 57%

Binge-Like Exposure to Ethanol Enhances Morphine's Anti-nociception in B6 Mice

Chang

Huang

Han³

et al. 2019

Front. Psychiatry

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“…These receptors are expressed on a variety of cells, facilitating rapid intervention in the event of an infection. It is believed that 99% of infections are responded to by the innate immune system [ 1 ]. The immune response can be divided into the following separate phases: homeostasis and surveillance; sensing and initiating the immune response (proinflammatory response); restoration of immune homeostasis and under certain physiological and pathological conditions, the generation of innate immune memory.…”

Section: Proinflammatory Immune Responsementioning

confidence: 99%

The Good and the Bad: Monocytes’ and Macrophages’ Diverse Functions in Inflammation

Austermann

Roth

Barczyk-Kahlert

2022

Cells

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Monocytes and macrophages are central players of the innate immune response and play a pivotal role in the regulation of inflammation. Thereby, they actively participate in all phases of the immune response, from initiating inflammation and triggering the adaptive immune response, through to the clearance of cell debris and resolution of inflammation. In this review, we described the mechanisms of monocyte and macrophage adaptation to rapidly changing microenvironmental conditions and discussed different forms of macrophage polarization depending on the environmental cues or pathophysiological condition. Therefore, special focus was placed on the tight regulation of the pro- and anti-inflammatory immune response, and the diverse functions of S100A8/S100A9 proteins and the scavenger receptor CD163 were highlighted, respectively. We paid special attention to the function of pro- and anti-inflammatory macrophages under pathological conditions.

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“…The innate immune system, responsible for the first encounter with a pathogen, can trigger adaptive immunity in case the initial response is ineffective. Both arms interact with each other, via cell-cell interactions and soluble factors maintaining a physiological steady state [ 5 ].…”

Section: Introduction: Where Innate and Adaptive Immunity Convergementioning

confidence: 99%

Blurring Borders: Innate Immunity with Adaptive Features

Kvell

Engelmann

et al. 2007

Clinical and Developmental Immunology

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Adaptive immunity has often been considered the penultimate of immune capacities. That system is now being deconstructed to encompass less stringent rules that govern its initiation, actual effector activity, and ambivalent results. Expanding the repertoire of innate immunity found in all invertebrates has greatly facilitated the relaxation of convictions concerning what actually constitutes innate and adaptive immunity. Two animal models, incidentally not on the line of chordate evolution (C. elegans and Drosophila), have contributed enormously to defining homology. The characteristics of specificity and memory and whether the antigen is pathogenic or nonpathogenic reveal considerable information on homology, thus deconstructing the more fundamentalist view. Senescence, cancer, and immunosuppression often associated with mammals that possess both innate and adaptive immunity also exist in invertebrates that only possess innate immunity. Strict definitions become blurred casting skepticism on the utility of creating rigid definitions of what innate and adaptive immunity are without considering overlaps.

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Bedeutung der angeborenen Immunantwort in der Sepsis

Cited by 11 publications

References 217 publications

Binge-Like Exposure to Ethanol Enhances Morphine's Anti-nociception in B6 Mice

Binge-Like Exposure to Ethanol Enhances Morphine's Anti-nociception in B6 Mice

The Good and the Bad: Monocytes’ and Macrophages’ Diverse Functions in Inflammation

Blurring Borders: Innate Immunity with Adaptive Features

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