Adiponectin Levels during the Septic Response to B. anthracis Sterne Strain in Baboons
HG Cohen, S Kurosawa, DJ Stearns-Kurosawa. Boston University School of Medicine, Boston, MA; College of Veterinary Sciences, Oklahoma State University, Stillwater, OK
Background: Adiponectin is a soluble mediator from white adipose tissue known to improve insulin sensitivity and have cardioprotective functions. During sepsis, dysfunctional insulin metabolism contributes to disease severity. During a septic response, however, the role of adiponectin is not clear and data are conflicting as to a protective or inflammatory role. Baboons are a validated animal model of sepsis and challenge with Gram positive Bacillus anthracis Sterne strain results in the pathophysiologic responses typical of sepsis. The question of whether changes in adiponectin levels corresponded to survival or an inflammatory response in this model were evaluated.
Design: Anesthetized baboons (Papio cynocephalus anubis; 6-8kg; n=13) were challenged by infusion with toxigenic Gram negative Bacillus anthracis Sterne strain (0.005-9.5 x 109 CFU/kg) using published methods (Am J Path 169:433, 2006). Blood was sampled at various time points and plasma was stored at -80oC until assayed. Adiponectin values were determined by ELISA (R&D Systems) that recognizes the globular domain of human adiponectin. Plasma TNF levels were determined by ELISA using published methods.
Results: Baseline adiponectin levels varied between animals with Mean SD = 40.717.7 ug/ml (Range 8.1- 77.9). Adiponectin levels did not correlate with TNF levels after challenge with B.anthracis Sterne strain. Increasing bacteria challenge led to increased TNF at T(2hrs) post-challenge, but adiponectin levels did not change significantly at <24hrs. With low challenge (<7x108CFU/kg) and modest inflammatory response, adiponectin levels increased 35-115% between day 1-7 post-challenge. Adiponectin levels at before challenge were not related to survival (p=0.19), but 7 day survivors had higher adiponectin levels than those who succumbed at 2-5 days (52.1 16.4 vs 33.4 14.7 ug/ml, p<0.05; n=12) despite similar bacterial challenge doses.
Conclusions: An early TNFa inflammatory response due to septic challenge did not result in corresponding changes in adiponectin levels, suggesting that release of adiponectin from adipose tissue may be regulated locally, but is not mediated by systemic TNF levels during sepsis. Adiponectin levels may play a role in a protective function late in the septic response because survivors tended to have higher adiponectin levels at day seven post-challenge. [NIH UO1AI075386 (SK)]
Monday, March 9, 2009 1:00 PM
Poster Session II # 203, Monday Afternoon