Evaluation of soluble IL-6 receptor concentration in serum and epithelial lining fluid from patients with interstitial lung diseases

Yokoyama, Akihito; Kohno, Nobuoki; Hirasawa, Yutaka; Kondo, Keiichi; Abe, Masahiro; Inoue, Yoshikazu; Fujioka, Seiji; Fujino, Shun; Ishida, Soshi; Hiwada, Kunio

doi:10.1111/j.1365-2249.1995.tb03672.x

Cited by 31 publications

(8 citation statements)

References 23 publications

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“…sIL-6r levels demonstrate an increased presence in many clinical conditions, such as interstitial lung disease and rheumatoid arthritis [61,62]. When complexed, sIL-6r and IL-6 have been shown to inhibit fibroblast proliferation, suggesting a possible anti-fibrotic function for the paired molecules [63].…”

Section: Soluble Interleukin Receptorsmentioning

confidence: 99%

Cytokine profiles in localized scleroderma and relationship to clinical features

Kurzinski

Torok

2011

Cytokine

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Localized scleroderma (LS) is a disfiguring autoimmune disease of the skin and underlying tissue that mainly affects the pediatric population. Inflammation of the tissue leads to fibrosis and atrophy, causing physical and psychological disability that can continue throughout childhood into adulthood. Available therapies for LS have had variable effects and are associated with morbidity themselves. A better understanding of the pathophysiology of LS, especially during the active inflammatory phase, would lead to more directed and efficacious therapies. As in systemic sclerosis (SSc), the other form of scleroderma, T-helper (Th) cells and their associated cytokines have been suggested to contribute significantly to the pathophysiology of LS supported by the presence of cytokines from these lineages in the sera and tissue of LS patients. It is postulated that the imbalance between Th1/Th2/Th17 cell subsets drives inflammation in the early stages of disease (Th1 and Th17 predominant) and fibrosis in the later stages of scleroderma (Th2 predominant). We review the available experimental data regarding cytokines in LS and compare them to available clinical disease severity and activity features. This provides the platform to launch further investigations into the role of select cytokines in the pathogenesis of LS and to provide directed therapeutic options in the future.

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Section: Soluble Interleukin Receptorsmentioning

confidence: 99%

Cytokine profiles in localized scleroderma and relationship to clinical features

Kurzinski

Torok

2011

Cytokine

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“…14 The latter study, however, showed that even after considering the confounding influences of obesity, patients with sleep apnea have higher morning soluble IL-6 receptor levels, a marker with more expansive physiologic effects than IL-6 alone and also reported to be elevated in inflammatory pulmonary conditions such as asthma and sarcoidosis. 15,16 The latter findings suggest that soluble IL-6 receptor signaling pathways may play a common role in the pathogenesis of both sleep apnea and asthma, potentially independent of obesity. …”

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confidence: 97%

Sleep apnea: A proinflammatory disorder that coaggregates with obesity

Mehra

Redline²

2008

Journal of Allergy and Clinical Immunology

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Both obesity and sleep apnea are prevalent health conditions that frequently coaggregate. Obesityassociated inflammation may influence asthma control; the relation of sleep apnea to asthma or allergic rhinitis may be bidirectional. Both obesity and sleep apnea are associated with augmented levels of inflammation and oxidative stress, and it is biologically plausible that the proinflammatory effects of one disorder influence the expression of the other disorder. This article elucidates mechanistic associations among obesity, sleep apnea, and systemic inflammation; highlights interrelationships between these factors with cardiopulmonary disease; and identifies specific areas for future research directions. KeywordsSleep apnea; obesity; inflammation; asthma Sleep apnea, characterized by loud snoring and daytime sleepiness, is a prevalent disorder, affecting upwards of 2% to 4% of the population. 1 It is caused by episodes of repetitive partial or complete upper airway collapse during sleep, which causes sleep disruption and fragmentation, as well as intermittent hypoxia, ventilatory overshoot hyperoxia, sympathetic nervous system surges, alterations in intrathoracic pressure, and local airway edema and inflammation. Sleep apnea also frequently coaggregates with obesity, and both conditions may independently or synergistically influence cardiopulmonary function and systemic inflammation. Moreover, sleep apnea and accompanying obesity may share common inflammatory pathways with asthma and allergic rhinitis. The relation of sleep apnea to asthma or allergic rhinitis may be bidirectional. To date, most research has been directed at understanding the links among sleep apnea, systemic inflammation, and cardiac responses. In this article, we present mechanistic associations between sleep apnea, obesity, and systemic inflammation. We highlight interrelationships between these factors and pulmonary as well as cardiac disease and identify specific areas for future research directions. Systemic responsesOne mechanism by which sleep apnea may contribute to systemic inflammation is through increased sympathetic nervous system activation, which may be induced by upper airway closure, hypoxia, hypercarbia, and/or arousals associated with the respiratory disturbances. Sleep apnea-related enhanced sympathetic nervous system activity likely plays a pathophysiologic role in the development of the acute increases in blood pressure commonly observed at the termination of apneas. It is also implicated in the pathogenesis of sustained systemic hypertension. Augmented sympathetic nervous system activity also appears to be associated with cytokine expression and oxidative stress. 2 In addition, elevated catecholamine levels may undergo auto-oxidation, and this has been considered to be a cause of catecholamine-induced cardiomyopathy, which may account for cardiovascular disease complications in individuals with sleep apnea.Cyclical episodes of hypoxia-reoxygenation, analogous to cardiac ischemia/reoxygenation injury, occur repetit...

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“…These studies led to the discovery that endothelial cells express receptor glycoprotein 130 (gp130 or CD130) on their surface in the absence of the IL-6R and thus require IL-6 soluble receptor (IL-6sR) to respond to IL-6 (47). IL-6sR is found in normal human serum (19) and significantly elevated levels are present during inflammation (62,70).…”

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confidence: 99%

Cholinergic agonists regulate JAK2/STAT3 signaling to suppress endothelial cell activation

Chatterjee

Al‐Abed

Sherry³

et al. 2009

American Journal of Physiology-Cell Physiology

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The cholinergic anti-inflammatory pathway is a physiological mechanism that inhibits cytokine production and minimizes tissue injury during inflammation. Previous investigations revealed that cholinergic stimulation (via cholinergic agonists and vagus nerve stimulation) suppresses endothelial cell activation and leukocyte recruitment. The purpose of this study was to investigate the mechanisms by which cholinergic agonists (e.g., nicotine and GTS-21) regulate endothelial cell activation. Specifically, we examined the effects of cholinergic agonists on IL-6-mediated endothelial cell activation through the JAK2/STAT3 signaling pathway. Treatment of macrovascular human umbilical vein endothelial cells (HUVECs) and microvascular endothelial cells (MVECs) with the cholinergic agonists nicotine and GTS-21 significantly reduced IL-6-mediated monocyte chemoattractant protein-1 (MCP-1) production and ICAM-1 expression which are regulated through the JAK2/STAT3 pathway. We found that treatment of endothelial cells with cholinergic agonists significantly reduced STAT3 activation by phosphorylation and DNA binding. The inhibition of STAT3 phosphorylation was reversed by sodium orthovanadate, an inhibitor of tyrosine phosphatases, as well as by NSC-87877 suggesting a SHP1/2-dependent mechanism. Further investigations showed that cholinergic agonists reduced the phosphorylation of JAK2, an upstream component of the JAK2/STAT3 pathway. Finally, we observed that nicotine and GTS-21 treatment decreased levels of SOCS3 (suppressor of cytokine signaling; a regulator of the inflammatory activity of IL-6) in activated endothelial cells. These data demonstrate that cholinergic agonists suppress IL-6-mediated endothelial cell activation through the JAK2/STAT3 pathway. Our results have significant implications for better understanding the therapeutic potential of cholinergic agonists for treating IL-6 mediated inflammatory conditions.

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Evaluation of soluble IL-6 receptor concentration in serum and epithelial lining fluid from patients with interstitial lung diseases

Cited by 31 publications

References 23 publications

Cytokine profiles in localized scleroderma and relationship to clinical features

Cytokine profiles in localized scleroderma and relationship to clinical features

Sleep apnea: A proinflammatory disorder that coaggregates with obesity

Cholinergic agonists regulate JAK2/STAT3 signaling to suppress endothelial cell activation

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