Exogenous Recombinant Adiponectin Improves Survival in Experimental Abdominal Sepsis

Year 2014, Volume: 31 Issue: 3, 244 - 248, 01.07.2014

Bülent Salman Tonguç Utku Yılmaz Tugan Tezcaner Ebru Ofluoğlu Demir Özge Tuğçe Paşaoğlu

Abstract

_Adiponectin, which has anti-inflammatory features, is an important substance in several metabolic mechanisms. Aims_ The aim of this study is to evauate the effects of exogenous intraperitoneal administration of adiponectin on the survival, intrabdominal adhesion and inflammatory cytokine levels in an experimental sepsis model. Study Design_ Animal experimentation. Methods_ Ninety rats were divided into a control group, adiponectin group and sham group. A cecal puncture abdominal sepsis model was performed in the adiponectin and control groups. Every three hours, exogenous adiponectin was administrated to the adiponectin group. At the 3rd and 24th hours, 10 rats were sacrified in each group in order to measure plasma tumor necrosis factor-α (TNF-α), interleukin (IL) 10, soluble intracellular adhesion molecule (ICAM)-1, IL-6 and macrophage inhibitory factor levels, and the activity of nuclear factor (NF)-kB. The remaining rats were followed for survival. Results_ The plasma levels of TNF-α, soluable ICAM-1, IL-6, and macrophage inhibitory factor were significantly higher in the control group than in the adiponectin and sham group (p_0.05). The increase in inflammatory cytokines with time was more prominent in the control group. The activity of NF-kB in the control group was higher than in the adiponectin group (p_0.05). The survival rate of the adiponectin group was higher than in the control group. Conclusion_ Administration of exogenous adiponectin to the peritoneum in abdominal sepsis increased survival and decreased intrabdominal adhesions by decreasing the inflammatory response_

Keywords

Adhesion, adiponectin, cytokine, sepsis, survival

References

• 1. Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet 2005;365:63-78. [CrossRef]
• 2. Bozza FA, Salluh JI, Japiassu AM, Soares M, Assis EF, Gomes RN, et al. Cytokine profiles as markers of disease severity in sepsis: A multiple analysis. Crit Care 2007;11:R49. [CrossRef]
• 3. Baugh JA, Bucala R. Macrophage migration inhibitory factor. Crit Care Med 2002;30:27-35. [CrossRef]
• 4. Bedirli A, Salman B, Pasaoglu H, Ofluoglu E, Sakrak O. Effects of nuclear faktor-kB ınhıbıtors on colon anastomıc healing rats. J Surg Res 2011;171:355-60. [CrossRef]
• 5. Ouchi N, Walsh K. Adiponectin as an anti-inflammatory factor. Clin Chim Acta 2007;380:24-30. [CrossRef]
• 6. Tsuchihashi H, Yamamoto H, Maeda K, Ugi S, Shimizu T, Endo Y, et al. Circulating concentrations of adiponectin, an endogenous lipopolysaccharide neutralizing protein, decrease in rats with polymicrobial sepsis. J Sur Res 2006;134:348-53. [CrossRef]
• 7. Uji Y, Yamamoto H, Tsuchihashi H, Maeda K, Funahashi T, Shimomura I, et al. Adiponectin deficiency is associated with severe polymicrobial sepsis, high inflammatory cytokine levels, and high mortality. Surgery 2009;145:550-7. [CrossRef]
• 8. Uji Y, Yamamoto H, Maeda K, Tsuchihashi H, Akabori H, Shimizu T, et al. Adiponectin deficiency promotes the production of inflammatory mediators while severely exacerbating hepatic injury in mice with polymicrobial sepsis. J Surg Res 2010;161:301-11. [CrossRef]
• 9. Arnalich F, Garcia-Palomero E, Lopez J, Jimenez M, Maderoo R, Renart J, et al. Predictive value of nuclear factor kB activity and plasma cytokine levels in patients with sepsis. Infect Immun 2000;68:1942-5. [CrossRef]
• 10. Söylemez N, Demirbağ R, Sezen Y, Yıldız A, Akpınar O. The levels of the leptin and adiponectin according to body mass index and their relationship with oxidative parameters. Anadolu Kardiyol Derg 2010;10:391-6. [CrossRef]
• 11. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, et al. Adiponectin, a new member of the family of solubale defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000;96:1723-32.
• 12. Maeda N, Takahashi M, Funahashi T,Kihara S, Nishizawa H, Kishida K, et al. PPAR gamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 2001;50:2094-9. [CrossRef]
• 13. Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, et al. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2003;301:1045-50. [CrossRef]
• 14. Teoh H, Quan A, Bang KW, Wang G, Lovren F, Vu V, et al. Adiponectin deficiency promotes endothelial activation and profoundly exacerbates sepsis-related mortality. Am J Pyhsiol Endocrinol Metab 2008;295:658-64. [CrossRef]
• 15. Ouchi N, Ohishi M, Kihara S, Funahashi T, Nakamura T, Nagaretani H, et al. Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension 2003;42:231-4. [CrossRef]
• 16. Gearing AJ, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993;14:506-12. [CrossRef]
• 17. Calandra T, Echtenacher B, Roy DL, Pugin J, Metz CN, Hültner L, et al. Protection from septic shock by neutralization of macrophage migration inhibitory factor. Nat Med 2000;6:164-70. [CrossRef]
• 18. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endoc Rev 2005;26:439-51. [CrossRef]