CCL23: a new CC chemokine involved in human brain damage.

Abstract

BACKGROUND:

CCL23 role in the inflammatory response after acute brain injuries remains elusive. Here, we evaluated whether CCL23 blood levels associate with acquired cerebral lesions and determined CCL23 predictive capacity for assessing stroke prognosis. We used preclinical models to study the CCL23 homologous chemokines in rodents, CCL9 and CCL6.

METHODS:

Baseline CCL23 blood levels were determined on 245 individuals, including ischaemic strokes (IS), stroke mimics and controls. Temporal profile of circulating CCL23 was explored from baseline to 24 h in 20 of the IS. In an independent cohort of 120 IS with a 3-month follow-up, CCL23 blood levels were included in logistic regression models to predict IS outcome. CCL9/CCL6 cerebral expression was evaluated in rodent models of brain damage. Both chemokines were also profiled in circulation and histologically located on brain following ischaemia.

RESULTS:

Baseline CCL23 blood levels did not discriminate IS, but permitted an accurate discrimination of patients presenting acute brain lesions (P = 0.003). IS exhibited a continuous increase from baseline to 24 h in circulating CCL23 (P < 0.001). Baseline CCL23 blood levels resulted an independent predictor of IS outcome at hospital discharge (ORadj : 19.702 [1.815-213.918], P = 0.014) and mortality after 3 months (ORadj : 21.47 [3.434-134.221], P = 0.001). In preclinics, expression of rodent chemokines in neurons following cerebral lesions was elevated. CCL9 circulating levels decreased early after ischaemia (P < 0.001), whereas CCL6 did not alter within the first 24 h after ischaemia.

CONCLUSIONS:

Although preclinical models do not seem suitable to characterize CCL23, it might be a novel promising biomarker for the early diagnosis of cerebral lesions and might facilitate the prediction of stroke patient outcome.

• Authors: A Simats, T García-Berrocoso, A Penalba, D Giralt, G Llovera, Y Jiang, L Ramiro, A Bustamante, E Martinez-Saez, F Canals, X Wang, A Liesz, A Rosell, J Montaner
• Journal: Journal of internal medicine (J Intern Med) Vol. 283 Issue 5 Pg. 461-475 (05 2018) ISSN: 1365-2796 [Electronic] England
• PMID: 29415332 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Association for the Publication of the Journal of Internal Medicine.

Chemical References

• Biomarkers
• CCL23 protein, human
• Ccl9 protein, mouse
• Chemokines
• Chemokines, CC
• Macrophage Inflammatory Proteins
• Ccl6 protein, mouse

Topics

• Aged
• Aged, 80 and over
• Animals
• Biomarkers (blood)
• Case-Control Studies
• Chemokines (metabolism)
• Chemokines, CC (blood)
• Disease Models, Animal
• Early Diagnosis
• Female
• Follow-Up Studies
• Humans
• Macrophage Inflammatory Proteins (blood)
• Male
• Mice, Inbred C57BL
• Neurons (metabolism)
• Neutrophils (metabolism)
• Prognosis
• Rats, Wistar
• Stroke (blood, diagnosis, mortality)
• Up-Regulation