D. A. Edelman1, D. M. Liberati1, L. N. Diebel1 1Wayne State University,Surgery/School Of Medicine,Detroit, MI, USA
Introduction: Obesity is an independent risk factor for ARDS and organ failure after severe trauma. Adipose tissue (AT) composed of adipocytes, macrophages, and other immune cells is a source of pro-inflammatory mediators that are associated with a chronic low grade inflammatory state in the obese patient. Obesity is also associated with activation of the sympathetic nervous system, which has been linked to shock induced gut and lung injury in the trauma setting. We hypothesized that sympathomimetic stimulation of adipose tissue would augment inflammatory signaling from adipose tissue and contribute to lung injury and ARDS after trauma.
Methods: Cell co cultures of mature adipocytes and macrophages (RAW264.7) were established and then incubated with either low or high concentrations of epinephrine (10-6 or 10-3 μM respectively). Cell culture supernatants (sup) were obtained at 12 hrs, and AT derived TNF α and IL-6 determined. In separate experiments, human microvascular endothelial cell (HMVEC) monolayers were incubated with adipocyte macrophage sup and HMVEC apoptosis (%apo), ICAM expression (MFI) and FITC-dextran permeability determined.
Results: No difference was seen in co culture data between the low dose epinephrine groups and the no dose epinephrine groups (p<0.001).
Conclusion: Both adipocytes and macrophages contribute to the "obesity related" proinflammatory state. Augmentation of this response after stress related sympathetic activation could contribute to lung injury and other remote organ failure in the injured obese patient. This response seems primarily due to stimulation of the adipocyte component of adipose tissue. The clinical impact likely depends on the magnitude of injury and the distribution/percent total body fat of the patient. Modification of the stress response following trauma may be a therapeutic target in this population.
