Immune response deviation and enhanced expression of chemokine receptor CCR4 in TBI patients due to unknown serum factors |
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Authors: | Dieter Cadosch Mohamed S Al-Mushaiqri Erwin Chan Allan P Skirving |
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Institution: | a School of Anatomy & Human Biology, University of Western Australia, Crawley, Australia b Department of Orthopaedic and Trauma Surgery, Royal Perth Hospital, Perth, Australia c Department of Surgery, State Hospital Winterthur, Winterthur, Switzerland d Department of Trauma Surgery, University of Zurich, Zurich, Switzerland |
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Abstract: | BackgroundSevere 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 methodsSerum 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.ResultsSerum 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).ConclusionPatients 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. |
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Keywords: | Traumatic brain injury Chemokines Cytokines Monocytes T-lymphocytes CCR4 |
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