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


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-alpha, while simultaneously increasing the secretion of immune-modulatory cytokines (IL-4, IL-10 and TGF-beta) (p<0.05).


CONCLUSIONS
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.
School of Anatomy & Human Biology, University of Western Australia, Crawley, Australia. dcadosch@gmx.net
Dieter
D
Cadosch
Mohamed S
MS
Al-Mushaiqri
Oliver P
OP
Gautschi
Erwin
E
Chan
Florian J
FJ
Jung
Allan P
AP
Skirving
Luis
L
Filgueira
D000293:Adolescent; D000328:Adult; D001930:Brain Injuries / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D019742:Chemokines, CC / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D050723:Fractures, Bone / Q000097:blood / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000097:blood* / Q000276:immunology; D011859:Radiography; D054398:Receptors, CCR4 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D015599:Trauma Severity Indices; D015854:Up-Regulation; D055815:Young Adult
D019742:Chemokines, CC; D054398:Receptors, CCR4