Interleukin-6 produced in subcutaneous adipose tissue is linked to blood pressure control in septic patients

Ikeoka, Dimas; Pachler, Christoph; Korsatko, Stefan; Mader, Julia K.; Weinhandl, Heinz; Bodenlenz, Manfred; Plank, Johannes; Smolle, Karl-Heinz; Ellmerer, Martin; Pieber, Thomas R.

doi:10.1016/j.cyto.2010.02.015

Cited by 13 publications

(5 citation statements)

References 28 publications

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“…Adipose tissue produces leptin, angiotensinogen, TNF‐α, IL‐6 and monocyte chemoattractant protein‐1, which all have the ability to contribute to vascular inflammation (Dandona et al . 2005; Paoletti et al ., 2006; Zhang and Zhang, 2009; Ikeoka et al . 2010).…”

Section: Discussionmentioning

confidence: 99%

Preserved arterial vasodilatation via endothelial protease-activated receptor-2 in obese type 2 diabetic mice

Kagota¹,

Chia

McGuire

2011

British Journal of Pharmacology

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BACKGROUND AND PURPOSEIn non-obese diabetic animals, protease-activated receptor-2 (PAR2) agonists are more effective vasodilators, which is attributed to increased COX-2 and endothelial NOS (eNOS) activities. Under conditions of diabetes and obesity, the effectiveness of PAR2 agonists is unknown. We compared the vasodilator responses of small calibre mesenteric arteries from obese diabetic B6.BKS(D)-Leprdb/J (db/db) induced by PAR2-activating agonists 2-furoyl-LIGRLO-amide (2fly) and trypsin to those obtained in controls [C57BL/6J (C57)], and assessed the contributions of COX, NOS and calcium-activated potassium channels (KCa) to these responses.EXPERIMENTAL APPROACHArteries mounted in wire myographs under isometric tension conditions were contracted submaximally by U46619 then exposed to vasodilators. mRNA and protein expression of PAR2, eNOS and soluble GC (sGC) were determined by real-time PCR and Western blots.KEY RESULTSACh- and nitroprusside-induced relaxations were attenuated in db/db compared with C57. In contrast, 2fly- and trypsin-induced relaxations were largely retained in db/db. A NOS inhibitor partly inhibited ACh- and 2fly-induced relaxations in C57, but not those in db/db. Inhibitors of the COX-cAMP pathway (FR122044, SC560, NS398, SC58125, SQ22536, CAY10441) did not affect these relaxation responses in either strain. Charybdotoxin (BKCa, SK3.1 blocker), but not iberiotoxin (BKCa blocker), inhibited responses to the PAR2 agonists in db/db. In db/db protein levels of eNOS were higher, whereas those of sGC were lower than in C57. PAR2 mRNA expression in db/db was higher than in C57.CONCLUSIONS AND IMPLICATIONSPAR2-mediated vasodilatation is protected against the negative effects of obesity and diabetes in mice. In diabetic vascular dysfunction, preserved PAR2 vasodilatation was linked to activation of SK3.1.

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Section: Discussionmentioning

confidence: 99%

Preserved arterial vasodilatation via endothelial protease-activated receptor-2 in obese type 2 diabetic mice

Kagota¹,

Chia

McGuire

2011

British Journal of Pharmacology

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“…As these pathogens infect adipocytes, we hypothesize that the inflammatory response observed in adipocytes may be associated with the latent infection of AT. In addition, IL-6 induces lipodystrophy [37] that likely favors the release of pathogens from AT into the circulation and, as a consequence, the induction of relapses. C. burnetii infection also induced the expression of the inflammatory genes within AT.…”

Section: Discussionmentioning

confidence: 99%

Persistence of Coxiella burnetii, the Agent of Q Fever, in Murine Adipose Tissue

et al. 2014

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Coxiella burnetii, the agent of Q fever, is known to persist in humans and rodents but its cellular reservoir in hosts remains undetermined. We hypothesized that adipose tissue serves as a C. burnetii reservoir during bacterial latency. BALB/c and C57BL/6 mice were infected with C. burnetii by the intraperitoneal route or the intracheal route. Adipose tissue was tested for the presence of C. burnetii several months after infection. C. burnetii was detected in abdominal, inguinal and dorsal adipose tissue 4 months post-infection, when no bacteria were detected in blood, liver, lungs and spleen, regardless of the inoculation route and independently of mouse strain. The transfer of abdominal adipose tissue from convalescent BALB/c mice to naïve immunodeficient mice resulted in the infection of the recipient animals. It is likely that C. burnetii infects adipocytes in vivo because bacteria were found in adipocytes within adipose tissue and replicated within in vitro-differentiated adipocytes. In addition, C. burnetii induced a specific transcriptional program in in-vivo and in vitro-differentiated adipocytes, which was enriched in categories associated with inflammatory response, hormone response and cytoskeleton. These changes may account for bacterial replication in in-vitro and chronic infection in-vivo. Adipose tissue may be the reservoir in which C. burnetii persists for prolonged periods after apparent clinical cure. The mouse model of C. burnetii infection may be used to understand the relapses of Q fever and provide new perspectives to the follow-up of patients.

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“…Using a microperfusion catheter inserted into the abdominal cutaneous adipose tissue of nine patients with severe sepsis, Ikeoka et al found that the concentrations of IL-1β, IL-6 and IL-8 were higher in subcutaneous adipose tissue than in serum, indicating a subcutaneous interstitial production of these pro-inflammatory mediators, remotely from the infection site [ 101 ]. In addition, blood pressure was negatively correlated with subcutaneous concentrations of IL-1β, IL-6 and IL-8.…”

Section: Interstitium-derived Inflammation (Local Production Of Media...mentioning

confidence: 99%

Role of the interstitium during septic shock: a key to the understanding of fluid dynamics?

Dargent,

Dumargne,

Labruyère

et al. 2023

j intensive care

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Background While not traditionally included in the conceptual understanding of circulation, the interstitium plays a critical role in maintaining fluid homeostasis. Fluid balance regulation is a critical aspect of septic shock, with a well-known association between fluid balance and outcome. The regulation of transcapillary flow is the first key to understand fluid homeostasis during sepsis. Main text Capillary permeability is increased during sepsis, and was classically considered to be necessary and sufficient to explain the increase of capillary filtration during inflammation. However, on the other side of the endothelial wall, the interstitium may play an even greater role to drive capillary leak. Indeed, the interstitial extracellular matrix forms a complex gel-like structure embedded in a collagen skeleton, and has the ability to directly attract intravascular fluid by decreasing its hydrostatic pressure. Thus, interstitium is not a mere passive reservoir, as was long thought, but is probably major determinant of fluid balance regulation during sepsis. Up to this date though, the role of the interstitium during sepsis and septic shock has been largely overlooked. A comprehensive vision of the interstitium may enlight our understanding of septic shock pathophysiology. Overall, we have identified five potential intersections between septic shock pathophysiology and the interstitium: 1. increase of oedema formation, interacting with organ function and metabolites diffusion; 2. interstitial pressure regulation, increasing transcapillary flow; 3. alteration of the extracellular matrix; 4. interstitial secretion of inflammatory mediators; 5. decrease of lymphatic outflow. Conclusions We aimed at reviewing the literature and summarizing the current knowledge along these specific axes, as well as methodological aspects related to interstitium exploration.

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Interleukin-6 produced in subcutaneous adipose tissue is linked to blood pressure control in septic patients

Cited by 13 publications

References 28 publications

Preserved arterial vasodilatation via endothelial protease-activated receptor-2 in obese type 2 diabetic mice

Preserved arterial vasodilatation via endothelial protease-activated receptor-2 in obese type 2 diabetic mice

Persistence of Coxiella burnetii, the Agent of Q Fever, in Murine Adipose Tissue

Role of the interstitium during septic shock: a key to the understanding of fluid dynamics?

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