INTERLEUKIN 12 AND INTERFERON-?? SYNTHETIC DEFICIENCY IS ASSOCIATED WITH DENDRITIC CELL CYTOPENIA AFTER CARDIAC SURGERY

• DOI: 10.1097/01.shk.0000167110.73129.a8
• Publication Date: 2005-06-28T10:38:21Z
• Authors: 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
• Keywords: 0301 basic medicine; Interleukins; Interleukin-18; Thoracic Surgery; Dendritic Cells; Interleukin-12; Interleukin-23; Recombinant Proteins; Interleukin-10; 3. Good health; Interferon-gamma; Protein Subunits; 03 medical and health sciences; Postoperative Complications; Neutralization Tests

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.