Diagnostic value of elevated CXCR4 and CXCL12 in neonatal sepsis

Tunç, Turan; Çekmez, Ferhat; Çetınkaya, Merih; Kalaycı, Tuğçe Özlem; Fidanci, Kursat; Saldır, Mehmet; Babacan, Oguzhan; Sarı, Erkan; Erdem, Galip; Çaycı, Tuncer; Kul, Mustafa; Kavuncuoğlu, Sultan

doi:10.3109/14767058.2014.916683

Cited by 19 publications

(38 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the CXCR4/CXCL12 axis has been shown to be of diagnostic as well as of overall importance in inflammation [ 19 , 33 , 34 ], the amount of serum CXCL12 was assessed. In the LPS-treated mice, CXCL12 levels continuously decreased up to 24 h after inflammation onset, followed by an increase at later time points.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive comparison of three different animal models for systemic inflammation

2017

View full text Add to dashboard Cite

BackgroundTo mimic systemic inflammation in humans, different animal models have been developed. Since these models are still discussed controversially, we aimed to comparatively evaluate the most widely used models with respect to the systemic effects, the influence on organ functions and to the underlying pathophysiological processes.MethodsSystemic inflammation was induced in C57BL/6N mice with lipopolysaccharide (LPS) treatment, peritoneal contamination and infection (PCI), or cecal ligation and puncture (CLP). Blood glucose and circulating cytokine levels were evaluated at 0, 2, 4, 6, 12, 24, 48, and 72 h after induction of inflammation. Additionally, oxidative stress in various organs and liver biotransformation capacity were determined. Markers for oxidative stress, apoptosis, infiltrating immune cells, as well as cytokine expression patterns, were assessed in liver and spleen tissue by immunohistochemistry.ResultsTreating mice with LPS and PCI induced a very similar course of inflammation; however, LPS treatment elicited a stronger response. In both models, serum pro-inflammatory cytokine levels rapidly increased whereas blood glucose decreased. Organs showed early signs of oxidative stress, and apoptosis was increased in splenic cells. In addition, liver biotransformation capacity was reduced and there was pronounced immune cell infiltration in both the liver and spleen. Mice exposed to either LPS or PCI recovered after 72 h. In contrast, CLP treatment induced comparatively fewer effects, but a more protracted course of inflammation.ConclusionsThe LPS model of systemic inflammation revealed to be most suitable when being interested in the impact of new therapies for acute inflammation. When using the CLP model to mimic human sepsis more closely, a longer time course should be employed, as the treatment induces delayed development of systemic inflammation.Electronic supplementary materialThe online version of this article (10.1186/s12929-017-0370-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultsmentioning

confidence: 99%

Comprehensive comparison of three different animal models for systemic inflammation

2017

View full text Add to dashboard Cite

show abstract

“…This impressively demonstrates the physiological importance of the CXCR4/CXCL12 axis. Recently, the diagnostic value has been shown in neonatal sepsis, where elevated CXCR4 and CXCL12 levels were accompanied by increased sepsis severity [ 11 ]. The involvement of the CXCR4/CXCL12 axis in autoimmune and inflammatory diseases is undisputed as treating rheumatoid arthritis, inflammatory bowel disease or lupus erythematodes with CXCR4-antagonists revealed beneficial outcomes [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Administration of a CXCL12 Analog in Endotoxemia Is Associated with Anti-Inflammatory, Anti-Oxidative and Cytoprotective Effects In Vivo

Seemann

Lupp

2015

PLoS ONE

View full text Add to dashboard Cite

BackgroundThe chemokine receptor CXCR4 is a multifunctional receptor which is activated by its natural ligand C-X-C motif chemokine 12 (CXCL12). As CXCR4 is part of the lipopolysaccharide sensing complex and CXCL12 analogs are not well characterized in inflammation, we aimed to uncover the systemic effects of a CXCL12 analog in severe systemic inflammation and to evaluate its impact on endotoxin induced organ damages by using a sublethal LPS dose.MethodsThe plasma stable CXCL12 analog CTCE-0214D was synthesized and administered subcutaneously shortly before LPS treatment. After 24 hours, mice were sacrificed and blood was obtained for TNF alpha, IFN gamma and blood glucose evaluation. Oxidative stress in the liver and spleen was assessed and liver biotransformation capacity was determined. Finally, CXCR4, CXCL12 and TLR4 expression patterns in liver, spleen and thymus tissue as well as the presence of different markers for apoptosis and oxidative stress were determined by means of immunohistochemistry.ResultsCTCE-0214D distinctly reduced the LPS mediated effects on TNF alpha, IFN gamma, ALAT and blood glucose levels. It attenuated oxidative stress in the liver and spleen tissue and enhanced liver biotransformation capacity unambiguously. Furthermore, in all three organs investigated, CTCE-0214D diminished the LPS induced expression of CXCR4, CXCL12, TLR4, NF-κB, cleaved caspase-3 and gp91 phox, whereas heme oxygenase 1 expression and activity was induced above average. Additionally, TUNEL staining revealed anti-apoptotic effects of CTCE-0214D.ConclusionsIn summary, CTCE-0214D displayed anti-inflammatory, anti-oxidative and cytoprotective features. It attenuated reactive oxygen species, induced heme oxygenase 1 activity and mitigated apoptosis. Thus, the CXCR4/CXCL12 axis seems to be a promising target in the treatment of acute systemic inflammation, especially when accompanied by a hepatic dysfunction and an excessive production of free radicals.

show abstract

“…In addition, neonates have delayed and impaired emergency granulopoiesis in response to sepsis compared with adults [26]. In sepsis, neonatal mice have delayed myelopoiesis related probably to an increased expression of C-X-C motif chemokine ligand 12 (CXCL12), which has been reported previously in human septic neonates [20,26,37]. The use of aluminium adjuvants suppresses CXCL12 expression in bone marrow, which correlates with the promotion of granulopoiesis [38].…”

Section: Discussionmentioning

confidence: 76%

Adjuvant pretreatment with alum protects neonatal mice in sepsis through myeloid cell activation

Rincón

Cuenca

Raymond

et al. 2017

Clinical and Experimental Immunology

View full text Add to dashboard Cite

The high mortality in neonatal sepsis has been related to both quantitative and qualitative differences in host protective immunity. Pretreatment strategies to prevent sepsis have received inadequate consideration, especially in the premature neonate, where outcomes from sepsis are so dismal. Aluminium salts-based adjuvants (alum) are used currently in many paediatric vaccines, but their use as an innate immune stimulant alone has not been well studied. We asked whether pretreatment with alum adjuvant alone could improve outcome and host innate immunity in neonatal mice given polymicrobial sepsis. Subcutaneous alum pretreatment improves survival to polymicrobial sepsis in both wild-type and T and B cell-deficient neonatal mice, but not in caspase-1/11 null mice. Moreover, alum increases peritoneal macrophage and neutrophil phagocytosis, and decreases bacterial colonization in the peritoneum. Bone marrow-derived neutrophils from alum-pretreated neonates produce more neutrophil extracellular traps (NETs) and exhibit increased expression of neutrophil elastase (NE) after in-vitro stimulation with phorbol esters. In addition, alum pretreatment increases bone marrow and splenic haematopoietic stem cell expansion following sepsis. Pretreatment of neonatal mice with an alum-based adjuvant can stimulate multiple innate immune cell functions and improve survival. These novel findings suggest a therapeutic pathway for the use of existing alum-based adjuvants for preventing sepsis in premature infants.

show abstract

Diagnostic value of elevated CXCR4 and CXCL12 in neonatal sepsis

Abstract: Serum CXCR4 and CXCL12 levels increase in septic neonates and that both chemokines decrease within 48-72 h of treatment. Serum concentrations of both chemokines represent promising novel biomarkers for neonatal sepsis.

Cited by 19 publications

References 27 publications

Comprehensive comparison of three different animal models for systemic inflammation

Comprehensive comparison of three different animal models for systemic inflammation

Administration of a CXCL12 Analog in Endotoxemia Is Associated with Anti-Inflammatory, Anti-Oxidative and Cytoprotective Effects In Vivo

Adjuvant pretreatment with alum protects neonatal mice in sepsis through myeloid cell activation

Contact Info

Product

Resources

About