| Autor: |
Yadavalli GK; Division of Infectious Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. gxy6@cwru.edu, Chien JW, Wener KM, Devecchio JL, Gupta S, Salata RA, Lee JH, Caldeira C, Auletta JJ, Heinzel FP |
| Jazyk: |
angličtina |
| Zdroj: |
Shock (Augusta, Ga.) [Shock] 2005 Jul; Vol. 24 (1), pp. 26-33. |
| DOI: |
10.1097/01.shk.0000167110.73129.a8 |
| Abstrakt: |
Traumatic or inflammatory injury associates with deactivation of monocytes and impaired synthesis of proinflammatory cytokines. We conducted a prospective, observational study to test whether cardiac surgery additionally impaired dendritic and natural killer (NK) cell functions responsible for innate immune production of interleukin (IL)-12-dependent interferon (IFN)-gamma in response to bacteria or toll-like receptor agonists. Blood samples were taken just before induction of anesthesia and 24 h postoperatively. LPS- and fixed Staphylococcus aureus-inducible IFNgamma synthesis in whole blood culture after surgery was reduced to 5% of preoperative values (P < 0.001). Production of IL-12 p70, a critical inducer of IFNgamma in the innate immune response, was reduced to 30% of that produced by preoperative samples (P = 0.013). Circulating CD11c, DR myeloid dendritic cells (DC) that are known sources of IL-12 p70 in normal blood, declined to approximately 25% of presurgical numbers (P = 0.004). Experimental depletion of CD11c, but not CD14, cells from normal peripheral blood mononuclear cell (PBMC) similarly disabled Staphylococcus aureus Cowan 1 (SAC)-induced production of IL-12 p70 and IFNgamma. Consistent with SAC-induced IFNgamma expression in CD56 NK and NK-T cells, CD56 depletion ablated IFNgamma production in normal whole blood. However, repletion of IL-12 p70, IL-18, IL-15, and IL-23 in postoperative blood failed to restore presurgical levels of IFNgamma synthesis (P < 0.05). We conclude that DC cytopenia after major surgery is sufficient to explain postoperative IL-12 p70 and IFNgamma synthetic deficiency. In addition, postoperative blood became hyporesponsive to IFNgamma-inducing cytokines as a further contribution to IFNgamma insufficiency. The novel finding of DC cytopenia after major surgery may portend a lack of other immunologic functions provided by this potent accessory cell population. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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