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1.
J Immunol ; 182(4): 2467-75, 2009 Feb 15.
Article in English | MEDLINE | ID: mdl-19201902

ABSTRACT

NKT cells have been described as innate regulatory cells because of their rapid response to conserved glycolipids presented on CD1d via their invariant TCR. However, little is known about the contribution of the hepatic NKT cell to the development of a local and/or systemic immune response to acute septic challenge (cecal ligation and puncture (CLP)). We found not only that mice deficient in invariant NKT cells (Jalpha18(-/-)) had a marked attenuation in CLP-induced mortality, but also exhibited an oblation of the systemic inflammatory response (with little effect on splenic/peritoneal immune responsiveness). Flow cytometric data indicated that following CLP, there was a marked decline in the percentage of CD3(+)alpha-galactosylceramide CD1d tetramer(+) cells in the mouse C57BL/6J and BALB/c liver nonparenchymal cell population. This was associated with the marked activation of these cells (increased expression of CD69 and CD25) as well as a rise in the frequency of NKT cells positive for both Th1 and Th2 intracellular cytokines. In this respect, when mice were pretreated in vivo with anti-CD1d-blocking Ab, we observed not only that this inhibited the systemic rise of IL-6 and IL-10 levels in septic mice and improved overall septic survival, but that the CLP-induced changes in liver macrophage IL-6 and IL-10 expressions were inversely effected by this treatment. Together, these findings suggest that the activation of hepatic invariant NKT cells plays a critical role in regulating the innate immune/systemic inflammatory response and survival in a model of acute septic shock.


Subject(s)
Inflammation/immunology , Liver/cytology , Liver/immunology , Natural Killer T-Cells/immunology , Shock, Septic/immunology , Animals , Antigen Presentation/immunology , Antigens, CD1d/immunology , Cytokines/blood , Cytokines/immunology , Flow Cytometry , Lymphocyte Activation/immunology , Macrophages/immunology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Mutant Strains , T-Lymphocytes/immunology
2.
J Trauma ; 59(6): 1396-9, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16394912

ABSTRACT

BACKGROUND: The National Emergency X-Radiography Utilization Study defined five criteria for obtaining cervical spine radiographic investigations in blunt trauma patients. Distracting injury was given as the indication for more than 30% of all x-ray studies ordered. The hypothesis of this study was that upper and lower torso injuries would have different effects on clinical cervical spine assessment. METHODS: This is a single-center, prospective, observational study of admitted, alert, adult blunt-trauma patients. All patients underwent cervical spine plain-film radiography. Data were collected on all injuries, physical examination findings, narcotic administration, and radiograph results. Patients with upper and lower torso injuries were compared in their ability complain of pain or midline tenderness relative to a cervical spine fracture. RESULTS: In all, 406 patients participated. All patients received narcotic analgesics before examination. Forty patients (9.9%) had cervical spine fractures, of whom seven had a nontender neck examination. All seven patients with a nontender cervical spine and a neck fracture had at least one upper torso injury. None of the 99 patients with injuries isolated to the lower torso and a nontender neck had a cervical spine fracture (p < 0.05). The frequency of cervical spine fracture among patients with cervical spine tenderness was 19.8% (n = 33). CONCLUSIONS: The National Emergency X-Radiography Utilization Study definition of a distracting injury may be narrowed. Upper torso injuries may be sufficiently painful to distract from a reliable cervical spine examination. Patients may detect spine tenderness in the presence of isolated painful lower torso injuries. Patients with spine tenderness warrant imaging.


Subject(s)
Cervical Vertebrae/injuries , Multiple Trauma/psychology , Perceptual Masking , Physical Examination , Spinal Fractures/diagnostic imaging , Wounds, Nonpenetrating/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neck Pain/diagnosis , Neck Pain/etiology , Pain Measurement , Prospective Studies , Radiography , Spinal Fractures/complications
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