Interleukin 12 and interferon-gamma synthetic deficiency is associated with dendritic cell cytopenia after cardiac surgery.
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.
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. gxy6@cwru.edu
Gopala K
GK
Yadavalli
Jason W
JW
Chien
Kenneth M
KM
Wener
Jennifer L
JL
Devecchio
Sameer
S
Gupta
Robert A
RA
Salata
Jai H
JH
Lee
Christiano
C
Caldeira
Jeffery J
JJ
Auletta
Frederick P
FP
Heinzel
D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency*; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000172:deficiency*; D020382:Interleukin-18 / Q000494:pharmacology; D053759:Interleukin-23; D007378:Interleukins / Q000494:pharmacology; D009500:Neutralization Tests; D011183:Postoperative Complications / Q000276:immunology; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000378:metabolism; D013903:Thoracic Surgery
D020382:Interleukin-18; D053759:Interleukin-23; D007378:Interleukins; D021122:Protein Subunits; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma