Interleukin 12 and interferon-γ synthetic deficiency is associated with dendritic cell cytopenia after cardiac surgery

Gopala K. Yadavalli, Jason W. Chien, Kenneth M. Wener, Jennifer L. DeVecchio, Sameer Gupta, Robert A. Salata, Jai H. Lee, Christiano Caldeira, Jeffery J. Auletta, Frederick P. Heinzel

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)26-33
Number of pages8
Issue number1
StatePublished - Jul 2005
Externally publishedYes


  • Dendritic cell
  • Endotoxin
  • Interferon-γ
  • Interleukin-12
  • Monocyte deactivation


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