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.
Yadavalli
Gopala K
GK
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. gxy6@cwru.edu
Chien
Jason W
JW
Wener
Kenneth M
KM
Devecchio
Jennifer L
JL
Gupta
Sameer
S
Salata
Robert A
RA
Lee
Jai H
JH
Caldeira
Christiano
C
Auletta
Jeffery J
JJ
Heinzel
Frederick P
FP
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