Adiponectin deficiency is associated with severe polymicrobial sepsis, high inflammatory cytokine levels, and high mortality

Uji, Yoshitaka; Yamamoto, Hiroshi; Tsuchihashi, Hiroshi; Maeda, Kazuhisa; Funahashi, Tohru; Shimomura, Iichirou; Shimizu, Tomoharu; Endo, Yoshihiro; Tani, Tohru

doi:10.1016/j.surg.2009.01.010

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Volume 145, Issue 5 , Pages 550-557, May 2009

Adiponectin deficiency is associated with severe polymicrobial sepsis, high inflammatory cytokine levels, and high mortality

Yoshitaka Uji, MD
- Department of Surgery, Shiga University of Medical Science, Shiga, Japan
Hiroshi Yamamoto, MD, PhD
- Department of Surgery, Shiga University of Medical Science, Shiga, Japan
- Reprint requests: Hiroshi Yamamoto, MD, PhD, Department of Surgery, Shiga University of Medical Science, Seta-tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Hiroshi Tsuchihashi, MD, PhD
- Department of Surgery, Shiga University of Medical Science, Shiga, Japan
Kazuhisa Maeda, MD, PhD
- Department of Metabolic Medicine, Graduate School of Osaka University, Osaka, Japan
Tohru Funahashi, MD, PhD
- Department of Metabolic Medicine, Graduate School of Osaka University, Osaka, Japan
Iichirou Shimomura, MD, PhD
- Department of Metabolic Medicine, Graduate School of Osaka University, Osaka, Japan
Tomoharu Shimizu, MD, PhD
- Department of Surgery, Shiga University of Medical Science, Shiga, Japan
Yoshihiro Endo, MD, PhD
- Department of Surgery, Shiga University of Medical Science, Shiga, Japan
Tohru Tani, MD, PhD
- Department of Surgery, Shiga University of Medical Science, Shiga, Japan

Accepted 23 January 2009. published online 23 March 2009.

Background

Adiponectin, a key substance in metabolic syndrome, is known to have anti-inflammatory properties. The relationship between adiponectin and sepsis in vivo is unclear. In this study, the possible involvement of adiponectin in polymicrobial sepsis was investigated using adiponectin-knockout (APN-KO) mice that underwent cecal ligation and puncture (CLP) and received the peroxisome proliferator-activated receptor gamma (PPAR-γ) that increases the plasma adiponectin concentration.

Methods

APN-KO and wild-type (WT) mice underwent either CLP or a sham operation. The plasma adiponectin, endotoxin, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) levels were determined before and at 2, 4, 6, 8, 12, 16, and 24 hours after the procedures, and the survival rates were compared. Mice were injected with rosiglitazone, a selective PPAR-γ agonist, and compared survival rates after CLP with those without rosiglitazone.

Results

After CLP, APN-KO mice had a significantly higher mortality than WT mice. The plasma endotoxin, TNF-α, and IL-6 levels in APN-KO mice were significantly higher than those in WT mice 24 hours after CLP. Within 4 hours after CLP, the plasma adiponectin level in WT mice decreased to half of the initial levels. Pre-CLP treatment with PPAR-γ was shown to increase the plasma adiponectin level and to improve significantly mortality of WT mice during sepsis; mortality among APN-KO mice did not improve.

Conclusion

These results suggest that adiponectin deficiency may cause the high mortality and the high inflammatory cytokine levels in mice with polymicrobial sepsis.