title: Delayed neutralization of interleukin 6 reduces organ injury, selectively suppresses inflammatory mediator, and partially normalizes immune dysfunction following trauma and hemorrhagic shock.
abstract: An excessive and uncontrolled systemic inflammatory response is associated with organ failure, immunodepression, and increased susceptibility to nosocomial infection following trauma. Interleukin 6 (IL-6) plays a particularly prominent role in the host immune response after trauma with hemorrhage. However, as a result of its pleiotropic functions, the effect of IL-6 in trauma and hemorrhage is still controversial. It remains unclear whether suppression of IL-6 after hemorrhagic shock and trauma will attenuate organ injury and immunosuppression. In this study, C57BL/6 mice were treated with anti-mouse IL-6 monoclonal antibody immediately prior to resuscitation in an experimental model combining hemorrhagic shock and lower-extremity injury. Interleukin 6 levels and signaling were transiently suppressed following administrations of anti-IL-6 monoclonal antibody following hemorrhagic shock and lower-extremity injury. This resulted in reduced lung and liver injury, as well as suppression in the levels of key inflammatory mediators including IL-10, keratinocyte-derived chemokine, monocyte chemoattractant protein 1, and macrophage inhibitory protein 1α at both 6 and 24 h. Furthermore, the shift to TH2 cytokine production and suppressed lymphocyte response were partly prevented. These results demonstrate that IL-6 is not only a biomarker but also an important driver of injury-induced inflammation and immune suppression in mice. Rapid measurement of IL-6 levels in the early phase of postinjury care could be used to guide IL-6-based interventions.
authors: *Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; and †Department of General Surgery, Union Hospital, Huazhong University of Science and Technology, China.
authors: Yong
authors: Y
authors: Zhang
authors: Jinxiang
authors: J
authors: Zhang
authors: Sebastian
authors: S
authors: Korff
authors: Faez
authors: F
authors: Ayoob
authors: Yoram
authors: Y
authors: Vodovotz
authors: Timothy R
authors: TR
authors: Billiar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006614:Hindlimb; D007108:Immune Tolerance / Q000187:drug effects; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008107:Liver Diseases / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D055370:Lung Injury / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013978:Tibial Fractures / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D000093242:Interleukin-6 Inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D018836:Inflammation Mediators; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors; C577686:interleukin-6, mouse