Immune response deviation and enhanced expression of chemokine receptor CCR4 in TBI patients due to unknown serum factors

• Published in: Injury Vol. 41; no. 6; pp. e4 - e9
• Main Authors: Cadosch, Dieter, Al-Mushaiqri, Mohamed S, Gautschi, Oliver P, Chan, Erwin, Jung, Florian J, Skirving, Allan P, Filgueira, Luis
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.06.2010
• Subjects: Adolescent; Adult; Brain Injuries - blood; Brain Injuries - diagnostic imaging; Brain Injuries - immunology; Case-Control Studies; CCR4; Cell Proliferation; Chemokines; Chemokines, CC - metabolism; Cytokines; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Fractures, Bone - blood; Fractures, Bone - immunology; Humans; Leukocytes, Mononuclear - metabolism; Male; Middle Aged; Monocytes; Multiple Trauma - blood; Multiple Trauma - immunology; Orthopedics; Radiography; Receptors, CCR4 - metabolism; T-lymphocytes; T-Lymphocytes - metabolism; Trauma Severity Indices; Traumatic brain injury; Up-Regulation; Young Adult; Monocytes; T-lymphocytes; Traumatic brain injury; Cytokines; CCR4; Chemokines
• ISSN: 0020-1383; 1879-0267
• DOI: 10.1016/j.injury.2009.09.001

Abstract Background Severe brain trauma leads to an activation of the immune system. To this date, neither the exact perturbation of the specific immune reaction induced by the traumatic brain injury (TBI), nor the interactions leading to the infiltration of peripheral immune cells into the brain are fully understood. Patients and methods Serum was collected from 17 patients with TBI and a long bone fracture, 24 patients with an isolated long bone fracture and from healthy individuals. The effect of the serum on normal human monocytes and T-lymphocytes was tested in vitro by assessing proliferation and expression of surface markers, chemokine receptors and cytokines. Results Serum collected from patients with a TBI and a long bone fracture increased the expression of the chemokine receptor CCR4 in monocytes when compared to patients with an isolated long bone fracture. Extending this comparison to T-lymphocytes, the serum from TBI patients induced lower proliferation rates and decreased expression of the pro-inflammatory cytokine TNF-α, while simultaneously increasing the secretion of immune-modulatory cytokines (IL-4, IL-10 and TGF-β) ( p < 0.05). Conclusion Patients with a TBI release currently unknown soluble factors into the circulating blood that up regulate expression of chemokine receptor CCR4 in peripheral blood monocytes whilst concurrently inducing expression of immunosuppressive cytokines by activated T-lymphocytes.