Effect of central administration of interleukin-1 receptor antagonist on protein synthesis in skeletal muscle, kidney, and liver during sepsis

Lloyd, Carolyn; Palopoli, Mary; Vary, Thomas C.

doi:10.1016/s0026-0495(03)00161-6

Cited by 13 publications

(7 citation statements)

References 26 publications

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“…Endogenous IL-1 signaling also plays a role in mediating protein catabolism, as i.c.v. infusion of IL-1Ra attenuates the loss of muscle mass in experimental sepsis models [30]. However, in order for this mechanism to be consistent with the presented data, the induction of hypothalamic IL-1β would have to be dependent on MyD88, yet its ultimate action on neurons is independent from MyD88.…”

Section: Discussionsupporting

confidence: 57%

Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β

Braun

Grossberg

Veleva-Rotse

et al. 2012

J Neuroinflammation

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BackgroundAnimals respond to inflammation by suppressing normal high-energy activities, including feeding and locomotion, in favor of diverting resources to the immune response. The cytokine interleukin-1 beta (IL-1β) inhibits normal feeding and locomotor activity (LMA) via its actions in the central nervous system (CNS). Behavioral changes in response to IL-1β are mediated by myeloid differentiation factor 88 (MyD88) in non-hematopoietic cells. It is unknown whether IL-1β acts directly on neurons or requires transduction by non-neuronal cells.MethodsThe Nestin-cre mouse was crossed with MyD88lox mice to delete MyD88 from neurons and glia in the CNS (MyD88ΔCNS). These mice were compared to total body MyD88KO and wild type (WT) mice. Mice had cannulae stereotactically placed in the lateral ventricle and telemetry transponders implanted into the peritoneum. Mice were treated with either intracerebroventricular (i.c.v.) IL-1β (10 ng) or vehicle. Food intake, body weight and LMA were continuously monitored for 24 h after treatment. I.c.v. tumor necrosis factor (TNF), a MyD88-independent cytokine, was used to control for normal immune development. Peripheral inflammation was modeled using intraperitoneal lipopolysaccharide (LPS). Groups were compared using two-way ANOVA with Bonferroni post-test. Efficacy of recombination was evaluated using tdTomato reporter mice crossed with the Nestin-cre mouse. MyD88 deletion was confirmed by Western blot.ResultsI.c.v. IL-1β treatment caused a significant reduction in feeding, body weight and LMA in WT mice. MyD88KO mice were protected from these changes in response to i.c.v. IL-1β despite having intact behavioral responses to TNF. Cre-mediated recombination was observed in neurons and astrocytes, but not microglia or endothelial cells. In contrast to MyD88KO mice, the behavioral responses of MyD88ΔCNS mice to i.c.v. IL-1β or intraperitoneal (i.p.) LPS were indistinguishable from those of WT mice.ConclusionSickness behavior is mediated by MyD88 and is dependent on the activity of cytokines within the brain. Our results demonstrate that MyD88 is not required in neurons or astrocytes to induce this behavioral response to IL-1β or LPS. This suggests that a non-Nestin expressing cell population responds to IL-1β in the CNS and transduces the signal to neurons controlling feeding and activity.

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Section: Discussionsupporting

confidence: 57%

Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β

Braun

Grossberg

Veleva-Rotse

et al. 2012

J Neuroinflammation

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“…IL-1 has been shown to induce inflammatory pain hyperalgesia (Watkins and Maier 2000), hypermetabolic state weight loss and anorexia (Hill et al 1996), adrenocortical response to surgical stress (DeKeyser et al 2000), and increased risk of postoperative ileus (Kalff et al 2003). IL-1ra can antagonize the above-mentioned IL-1-mediated effects (Cunha et al 2000;Goshen et al 2003;Lloyd et al 2003;Plaza et al 1997), including weight loss and anorexia (Josephs et al 2000); thus, the anti-inflammatory effects of IL-1ra may contribute to a better postoperative recovery.…”

Section: Perioperative Analgesia and Recoverymentioning

confidence: 99%

Postoperative Pain Management and Proinflammatory Cytokines: Animal and Human Studies

Shavit

Fridel

Beilin

2006

Jrnl Neuroimmune Pharm

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The postoperative period is associated with neuroendocrine, metabolic, and immune alterations, which are the combined result of tissue damage, anesthesia, postoperative pain, and psychological stress. Limited evidence indicates that pain management in the postoperative period can affect the outcome of the surgery, reducing cardiac, pulmonary, and metabolic complications. Recent evidence indicates that pain and immune factors, especially proinflammatory cytokines, mutually interact and influence each other. A series of animal studies demonstrates that effective preemptive analgesia improved postoperative recovery, and this effect was enhanced by coadministration of IL-1ra together with the preemptive analgesics. Furthermore, preemptive analgesia attenuated surgery-induced PGE(2) production in the amygdala and the activation of the HPA axis. IL-1 signaling is required for the production of amygdala PGE(2) in response to surgical stress, and may thus affect the physiological and psychological aspects of surgical stress. These reports suggest that short-term effective analgesia can have long-lasting beneficial effects on surgery recovery. They further suggest that IL-1 blockade should be considered in the clinical management of pain associated with peripheral or nerve injury. Another series of human studies describes an interaction between the effectiveness of postoperative pain relief and surgery-associated immune alterations: In three separate studies, the more effective pain management technique was associated with diminished surgery-induced immune alterations, especially diminished elevation of IL-1. Reduced elevation of postoperative IL-1 and effective pain relief may both contribute to an attenuated illness response and a better surgery outcome.

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“…Multiple inflammatory cytokines are induced in the hypothal ami of animals treated peripherally with LPS (Ogimoto et al, 2006) or in tumorbearing animals (Ropelle et al, 2007). When CNS IL1 receptors are pharmacologically antagonized during systemic inflammation, anorexia and alterations in peripheral protein metabolism are ameliorated (Layé et al, 2000;Lloyd et al, 2003), suggesting that CNS inflammation plays a critical role in integrating the host response to disease.…”

mentioning

confidence: 99%

Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic–pituitary–adrenal axis

Braun

Zhu

Szumowski

et al. 2011

Journal of Experimental Medicine

180

189

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Effect of central administration of interleukin-1 receptor antagonist on protein synthesis in skeletal muscle, kidney, and liver during sepsis

Cited by 13 publications

References 26 publications

Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β

Expression of myeloid differentiation factor 88 in neurons is not requisite for the induction of sickness behavior by interleukin-1β

Postoperative Pain Management and Proinflammatory Cytokines: Animal and Human Studies

Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic–pituitary–adrenal axis

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