Serum concentrations of activin and follistatin are elevated and run in parallel in patients with septicemia

Michel, Uwe; Ebert, Sandra; Phillips, David J.; Nau, Roland

doi:10.1530/eje.0.1480559

Cited by 86 publications

(62 citation statements)

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“…A similar pattern of expression during infections has been observed for other immunomodulatory cytokines, such as IL-10 and transforming growth factor-β 1 (27). In agreement with our findings, other studies have demonstrated that activin-A is elevated in the circulation during septicemia in adults and associated with the severity of inflammation (28). Moreover, activin-A is increased in the cerebrospinal fluid during meningitis in animal models and adults (22,23).…”

Section: Discussionsupporting

confidence: 90%

“…Moreover, activin-A is increased in the cerebrospinal fluid during meningitis in animal models and adults (22,23). Serum levels of activin-A vary with certain studies reporting high levels (11,29) and other studies reporting similar levels, or even, reporting lower levels to our study (9,28,30,31). This discordance could be due to the differences in the experimental set up, including the age of the neonates studied, the disease context, the methodology employed, the time point of analysis, etc.…”

Section: Discussionmentioning

confidence: 54%

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Activin-A exerts a crucial anti-inflammatory role in neonatal infections

et al. 2013

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Background: Activin-A is a cytokine with a critical role in infections and associated inflammation in experimental models and humans. Still, the effects of activin-A on neonatal infections remain elusive. Here, we investigated the expression of activin-A in the serum of septicemic preterm and term neonates and in peripheral blood leukocytes stimulated with inflammatory agents in vitro. The role of activin-A in the regulation of inflammatory responses by neonatal leukocytes was delineated. Methods: Peripheral blood was obtained from 37 septicemic neonates between the first and fifth days postinfection and from 35 healthy controls. Isolated monocytes and lymphocytes were stimulated with lipopolysaccharide (LPS) or phytohemagglutinin (PHA) in vitro in the presence of activin-A. Cell proliferation, cytokine, and chemokine release were investigated. results: Activin-A was significantly increased in the serum of preterm septicemic neonates. Neonatal leukocytes secreted copious amounts of activin-A following stimulation, pointing to these cells as an essential source of activin-A in the circulation. Of note, treatment of neonatal leukocytes with activin-A during PHA and LPS stimulation resulted in significantly decreased interleukin (IL)-1β, IL-6, and CXCL8 production, concomitant with a striking increase in the anti-inflammatory mediator, IL-10. conclusion: Our findings uncover activin-A as a novel immunomodulatory agent critical for the control of inflammatory responses in septicemic neonates.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 54%

Activin-A exerts a crucial anti-inflammatory role in neonatal infections

et al. 2013

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“…[35][36][37][38][39] Accordingly, elevated activin A levels have been observed in a mouse model of endotoxemia and in patients with clinical sepsis condition. 22,40 Furthermore, treatment with FS increased the survival of mice that were lethally challenged with LPS, 22 supporting the role of activin A as an early proinflammatory mediator in these models.…”

Section: Monocytesmentioning

confidence: 87%

When versatility matters: activins/inhibins as key regulators of immunity

Alemán-Muench

Soldevila

2011

Immunol Cell Biol

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Activins and inhibins are members of the transforming growth factor-b superfamily that have been considered crucial regulators of cell processes, such as differentiation, proliferation and apoptosis, in different cell types. Initial studies about the function of activin A in the immune system focused on the regulation of hematopoiesis in the bone marrow under homeostatic and inflammatory conditions. Recent data provide a more comprehensive understanding about the role of activins/inhibins in the immune system. Novel findings included in this review point out the important requirement of activin/inhibin signaling to maintain the balance between homeostatic and inflammatory signals that are required for the optimal development and function of immune cells. The purpose of this review is to highlight the versatile nature of activins/inhibins as key regulators of both the innate and adaptive immune responses. Keywords: activin; inhibin; inflammation; immune cells; immunity; tolerance Activins and inhibins are members of the transforming growth factor-b (TGF-b) superfamily that were initially described as regulators of reproductive processes in mammals, and were first named after their positive and negative effect in the release of follicle-stimulating hormone from the pituitary gland, respectively. 1 These dimeric ligands have been shown to modulate a variety of cellular functions such as apoptosis, proliferation, differentiation, cellular migration, among others. 2,3 Activin A (bA/bA) is the best-characterized ligand of this subfamily, although there are other bioactive forms, activin B (bB/bB) and activin AB (bA/bB), which differ in their potency and cellular function. 4 Activin A is a molecule with pleiotropic functions, which shares with TGF-b the SMAD2/3 canonical signaling pathway (reviewed by Shi and Massague 5 ) but uses distinct type II (ActRIIs) and type I (ALK2, ALK4 and ALK7) receptors. [6][7][8][9] The biological function of activins can be blocked by follistatin (FS), a glycoprotein that binds activin A with high affinity, functioning as a ligand trap. 10 On the other hand, inhibins are heterodimers formed by uncommon a-and b-subunits and exist in two isoforms, inhibin A (a/bA) and B (a/bB). Inhibins have been shown to antagonize activinmediated functions by a mechanism that involves binding to b-glycan (TGFbRIII) and formation of a ternary complex with ActRIIs. As a consequence, activin type I receptors (ALK4 and ALK2) are excluded from the receptor complex, leading to the inhibition of SMADmediated signaling. 3,[11][12][13][14] Despite the fact that inhibins have been classically considered as activin antagonists, there is evidence showing that they do not always antagonize activin-mediated functions in several cell types, suggesting the existence of an independent inhibinmediated signaling pathway. 3 Compelling evidence has shown that activins also regulate various non-reproductive processes, such as mesoderm induction, liver proliferation, skin morphogenesis, erythropoiesis, bone formation, neu...

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“…In animals, ActA increases quickly in circulation in response to acute inflammatory stimulus, such as an lipopolysaccharide (LPS) injection 34. In humans, elevated ActA levels have been observed in several inflammatory diseases, such as septicemia35 or acute distress syndrome,36 and are associated with the severity of the disease and poor prognosis. Neoplastic process is associated with systemic inflammation, mediated by several cytokines such as IL‐1β, IL‐6, TNFα, and ActA 37, 38.…”

Section: Discussionmentioning

confidence: 99%

Circulating Activin A predicts survival in cancer patients

Loumaye

Barsy

Nachit

et al. 2017

J cachexia sarcopenia muscle

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BackgroundSeveral experimental evidences pinpoint the possible role of Activin A (ActA) as a driver of cancer cachexia. Supporting this hypothesis, we showed recently that human cancer cachexia is associated with high ActA levels. Moreover, ActA levels were correlated with body weight loss and skeletal muscle density, two prognostic factors in cancer patients. Our goal was therefore to investigate the value of ActA to predict survival in cancer patients.MethodsPatients with colorectal or lung cancer were prospectively enrolled at the time of diagnosis or relapse between January 2012 and March 2014. At baseline, patients had clinical, nutritional, and functional assessment. Body composition and skeletal muscle density were measured by CT scan, and plasma ActA concentrations were determined. Overall survival (OS) was analysed since inclusion to 24 months later.ResultsSurvival data were available for 149 patients out of 152. Patients with high ActA (≥408 pg/mL) had lower OS than those with low levels, regardless the type of cancer (OS in colorectal cancer, 50% vs. 79%, P < 0.05; and in lung cancer, 27% vs. 67%, P = 0.001). The multivariable analysis confirmed the prognostic value of ActA independently of tumour stage or inflammatory markers, particularly in lung cancer. Low muscularity was also an independent prognostic factor.ConclusionsOur study demonstrates that high ActA level is an independent prognosis factor of survival in cancer patients. More than a basic marker of the severity of the neoplastic disease or of the inflammatory process, ActA seems to influence survival by contributing to the development of cachexia and loss of skeletal muscle mass.

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Serum concentrations of activin and follistatin are elevated and run in parallel in patients with septicemia

Cited by 86 publications

References 51 publications

Activin-A exerts a crucial anti-inflammatory role in neonatal infections

Activin-A exerts a crucial anti-inflammatory role in neonatal infections

When versatility matters: activins/inhibins as key regulators of immunity

Circulating Activin A predicts survival in cancer patients

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