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.
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.
Authors: Natasha Spottiswoode; Andrew E Armitage; Andrew R Williams; Alex J Fyfe; Sumi Biswas; Susanne H Hodgson; David Llewellyn; Prateek Choudhary; Simon J Draper; Patrick E Duffy; Hal Drakesmith Journal: Infect Immun Date: 2017-11-17 Impact factor: 3.441