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Physiological effects of modulating the interleukin-6 axis.

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TLDR
This work has shown that pharmacologic modulation of the IL-6 axis is a rational therapeutic approach; however, multiple predictable, but often underappreciated, effects on tissues and organs beyond the blood vessels may also occur.
Abstract
IL-6 is a pleiotropic cytokine involved in many biological functions that affect tissues beyond the immune system and the vasculature. This multifunctional cytokine exerts its actions via the classic signalling pathway when it binds to the transmembrane IL-6 receptor (IL-6R) or via the trans-signalling pathway upon binding to the soluble form of IL-6R (sIL-6R). In general, classic IL-6 signalling is responsible for the anti-inflammatory properties of IL-6, whereas trans-signalling is responsible for the pro-inflammatory actions of IL-6. As a result, dysregulation of the IL-6 axis can lead to the onset or development of several disease states, particularly autoimmune and inflammatory disorders, including RA and GCA. This pathological role of IL-6 means that pharmacologic modulation of the IL-6 axis is a rational therapeutic approach; however, multiple predictable, but often underappreciated, effects on tissues and organs beyond the blood vessels may also occur.

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Citations
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Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection.

TL;DR: Following viral clearance and clinical recovery, at 1 month after infection with influenza, mice are better protected from Streptococcus pneumoniae infection due to a population of monocyte-derived alveolar macrophages that produce increased interleukin-6.
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The complement system drives local inflammatory tissue priming by metabolic reprogramming of synovial fibroblasts.

TL;DR: In this paper, the molecular and cellular mechanisms of inflammatory tissue priming are defined and the checkpoints between remission and persistence remain unknown. But, they suggest possibilities for therapeutic intervention abrogating tissue pre-priming without immunosuppression.
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Neuraxial Cytokines in Pain States.

TL;DR: Current thinking suggests that cytokines by this action throughout the neuraxis play key roles in the induction of pain and the maintenance of the facilitated states of pain behavior generated by tissue injury/inflammation and nerve injury.
References
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IL-6 in Inflammation, Immunity, and Disease

TL;DR: The mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.
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The pro- and anti-inflammatory properties of the cytokine interleukin-6

TL;DR: It turns out that regenerative or anti-inflammatory activities of interleukin-6 are mediated by classic signaling whereas pro-inflammatory responses of interLEukin -6 are rather mediated by trans-signaling.
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Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress.

TL;DR: CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above.
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The Hypothalamic–Pituitary–Adrenal Axis and Immune-Mediated Inflammation

TL;DR: Celsus described four of the five cardinal signs of inflammation 2000 years ago, and Eustachio discovered the adrenal glands almost 500 years ago; but not until 1936 did Selye note that in rats exposed to stressors, the adrenAL glands were enlarged, and the thymus and lymph nodes shrunken.
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Trending Questions (2)
Why does IL-6 has proinflammatory and anti-inflammatory actions?

IL-6 has pro-inflammatory actions through trans-signaling and anti-inflammatory actions through classic signaling pathways.

Does Interleukin-6 (IL-6) exhibits immune-modulating effects capable of perturbing immune regulation and promoting autoimmune thyroiditis?

IL-6 exhibits immune-modulating effects that can disrupt immune regulation, potentially contributing to the development of autoimmune diseases.