TY - JOUR
T1 - Interleukin 12 and interferon-γ synthetic deficiency is associated with dendritic cell cytopenia after cardiac surgery
AU - Yadavalli, Gopala K.
AU - Chien, Jason W.
AU - Wener, Kenneth M.
AU - DeVecchio, Jennifer L.
AU - Gupta, Sameer
AU - Salata, Robert A.
AU - Lee, Jai H.
AU - Caldeira, Christiano
AU - Auletta, Jeffery J.
AU - Heinzel, Frederick P.
PY - 2005/7
Y1 - 2005/7
N2 - 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)-γ 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 IFNγ 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 IFNγ 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 IFNγ. Consistent with SAC-induced IFNγ expression in CD56+ NK and NK-T cells, CD56 depletion ablated IFNγ 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 IFNγ synthesis (P < 0.05). We conclude that DC cytopenia after major surgery is sufficient to explain postoperative IL-12 p70 and IFNγ synthetic deficiency. In addition, postoperative blood became hyporesponsive to IFNγ-inducing cytokines as a further contribution to IFNγ 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.
AB - 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)-γ 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 IFNγ 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 IFNγ 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 IFNγ. Consistent with SAC-induced IFNγ expression in CD56+ NK and NK-T cells, CD56 depletion ablated IFNγ 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 IFNγ synthesis (P < 0.05). We conclude that DC cytopenia after major surgery is sufficient to explain postoperative IL-12 p70 and IFNγ synthetic deficiency. In addition, postoperative blood became hyporesponsive to IFNγ-inducing cytokines as a further contribution to IFNγ 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.
KW - Dendritic cell
KW - Endotoxin
KW - Interferon-γ
KW - Interleukin-12
KW - Monocyte deactivation
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U2 - 10.1097/01.shk.0000167110.73129.a8
DO - 10.1097/01.shk.0000167110.73129.a8
M3 - Article
C2 - 15988317
AN - SCOPUS:21744459078
SN - 1073-2322
VL - 24
SP - 26
EP - 33
JO - Shock
JF - Shock
IS - 1
ER -