Effect of Vasoactive Intestinal Peptide (VIP) on Cytokine Levels and Haemostatic and Biochemical Parameters in A Rat Endotoxaemic Model

Col, Ramazan; Durgun, Zafer

doi:10.2478/v10213-012-0012-6

Abstract

The presented study was planned to determine whether vasoactive intestinal peptide (VIP) could prevent cytokine haemostatic, haematological, and biochemical disturbances in LPS-treated rats. Adult male Wistar rats (weight range: 200-250 g) were used. The study included four groups: group 1 served as a control group (C); animals in group 2 were given intravenously 1.6 mg/100 g of LPS (E. coli, serotype 0.111:B4); in group 3, rats were injected intraperitoneally with 25 ng/kg of VIP; in group 4, the same doses of VIP and LPS were injected simultaneously. Blood samples were collected 6 h after treatments. In endotoxaemic rats, platelet count, fibrinogen, and antithrombin levels were decreased, the activated partial thromboplastin time and prothrombin time were prolonged, and leucopoenia, as well as significant changes in differential leukocyte percentage were demonstrated. In addition, LPS caused statistically significant increases in plasma TNF- , IL-6, and IL-10 levels, and AST, ALT, creatinine, cholesterol, triglyceride concentrations. However, it caused a statistically significant decrease in total protein and albumin levels when compared to control group. The results showed that during endotoxaemia, VIP had moderately therapeutic effect as an antiinflammatory agent, suppressing TNF-α and IL-6, and stimulating IL-10; however, it was not effective against the adverse effect of LPS on investigated haematological and biochemical parameters.

References

1. Al-Dughaym A.M.: Some endotoxin-induced clinical and biochemical changes in plasma of camels (Camelusdromedaricus). Vet Res Commun 2004, 28, 711-718.10.1023/B:VERC.0000045956.68656.43
Search in Google Scholar
2. Allam G.: Vasoactive intestinal peptide inhibits liver pathology in acute murine Schistosomiasis mansoni and modulates IL-10, IL-12 and TNF-1 production. Immunobiology 2007, 212, 603-612.10.1016/j.imbio.2007.05.00617869638
Search in Google Scholar
3. Asakura H., Asamura R., Ontachi Y., Hayashi T., Yamazaki M., Morishita E., Miyamoto K.I., Nakao S.: Selective inducible nitric oxide synthase inhibition attenuates organ dysfunction and elevated endothelin levels in LPS-induced DIC model rats. J Thromb Haemost 2005, 3, 1050-1055.10.1111/j.1538-7836.2005.01248.x15869603
Search in Google Scholar
4. Col R., Keskin E., Atalay B.: Effect of pentoxifylline on endotoxin-induced haemostatic disturbances in rabbits. Acta Vet Hung 2005, 53, 325-335.10.1556/avet.53.2005.3.616156128
Search in Google Scholar
5. Delgado M., Martinez C., Pozo D., Calvo J.R., Leceta J., Ganea D., Gomariz R.P.: Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activation polypeptide (PACAP) protect mice from lethal endotoxemia through the inhibition of TNF-a and IL-6. J Immunol 1999, 162, 1200-1205.10.4049/jimmunol.162.2.1200
Search in Google Scholar
6. Delgado M., Pozo D., Martinez C., Leceta J., Calvo J.R., Ganea D., Gomariz R.P.: Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit endotoxin-induced TNF-a production by macrophages, in vitro and in vivo studies. J Immunol 1999, 162, 2358-2367.10.4049/jimmunol.162.4.2358
Search in Google Scholar
7. Dhuley J.N., Naik S.R.: Effect of rhinax on bacterial lipopolysaccharide induced endotoxemia in rats. Indian J Exp Biol 1998, 36, 315-317.
Search in Google Scholar
8. Fernández-Martínez E., Morales-Ríos M.S., Pérez- Alvarez V., Muriel P.: Immunomodulatory effects of thalidomide analogs on LPS-induced plasma and hepatic cytokines in the rat. Biochem Pharmacol 2004, 68, 1321-1329.10.1016/j.bcp.2004.06.01815345321
Search in Google Scholar
9. Fourrier F., Chopin C., Huart J.J., Runge I., Caron C., Goudemand J.: Double-blind placebo-controlled trial of antithrombin III concentrate in septic shock with disseminated intravascular coagulation. Chest 1993, 104, 882-892.10.1378/chest.104.3.8828365305
Search in Google Scholar
10. Fraunberg P., Schaefer S., Werdan K., Walli A.K., Seidel D.: Reduction of circulating cholesterol and apoliloprotein levels during sepsis. Clin Chem Lab Med 1999, 37, 357-362.10.1515/CCLM.1999.05910353483
Search in Google Scholar
11. Gaviria J.M., Dale D.C., Root R.K.: Neutrophils: function and role in sepsis syndrome. Sepsis 1998, 2, 107-117.10.1023/A:1009717806924
Search in Google Scholar
12. Gonzalez-Rey E., Delgado M.: Vasoactive intestinal peptide and regulatory T-cell induction: a new mechanism and therapeutic potential for immune homeostasis. Trends Mol Med 2007, 13, 241-251.10.1016/j.molmed.2007.04.00317467339
Search in Google Scholar
13. Grimm M.C., Newman R., Hassim Z., Cuan N., Connor S.J., Le Y., Wang J.M., Oppenheim J.J., Lloyd A.R.: Cutting edge: vasoactive intestinal peptide acts as a potent suppressor of inflammation in vivo by transdeactivating chemokine receptors. J Immunol 2003, 171, 4990-4994.10.4049/jimmunol.171.10.499014607894
Search in Google Scholar
14. Hayashi T., Kishiwada M., Fujii K., Yuasa H., Nishioka J., Ido M., Gabazza E.C., Suzuki K.: Lipopolysaccharide-induced decreased protein S expression in liver cells is mediated by MEK/ERK signaling and NFjB activation: involvement of membrane-bound CD14 and toll-like receptor-4. J Thromb Haemost 2006, 4, 1763-1773.10.1111/j.1538-7836.2006.02042.x16879219
Search in Google Scholar
15. Hopper K., Bateman S.: An updated view of hemostasis: mechanisms of hemostatic dysfuntion associated with sepsis. J Vet Emerg Crit Care 2005, 15, 83-91.10.1111/j.1476-4431.2005.00128.x
Search in Google Scholar
16. Iba T., Nakarai .E, Takayama T., Nakajima K., Sasaoka T., Ohno Y.: Combination effect of antithrombin and recombinant human soluble thrombomodulin in a lipopolysaccharide induced rat sepsis model. Crit Care 2009, 13, R203.10.1186/cc8210281190120003418
Search in Google Scholar
17. Izutani W., Fujita M., Nishizawa K., Koga J.: Urinary protein C inhibitor as a therapeutic agent to disseminated intravascular coagulation (DIC): A comparison with low molecular weight heparin in rats with lipopolysaccharide-induced DIC. Biol Pharm Bull 2000, 23, 1046-1050.10.1248/bpb.23.104610993202
Search in Google Scholar
18. Lauw F.N., Pajkrt D., Hack C.E., Kurimoto M., van Deventer S.J.H., van der Poll T.: Proinflammatory effects of IL-10 during human endotoxemia. J Immunol 2000, 165, 2783-2789.10.4049/jimmunol.165.5.278310946310
Search in Google Scholar
19. Levi M., de Jonge E., van der Poll T.: Rationale for restoration of physiological anticoagulant pathways in patients with sepsis and disseminated intravascular coagulation. Crit Care Med 2001, 29, 90-94.10.1097/00003246-200107001-0002811445740
Search in Google Scholar
20. Mathiak G., Grass G., Herzmann T., Luebke T., Zetina C.C., Boehm S.A., Bohlen H., Neville L.F., Hoelscher A.H.: Caspase-1-inhibitor ac-YVAD-cmk reduces LPSlethality in rats without affecting haematology or cytokine responses. Br J Pharmacol 2000, 131, 383-386.10.1038/sj.bjp.0703629157236911015286
Search in Google Scholar
21. Møller S., Laigaard F., Olgaard K., Hemmingsen C.: Effect of 1,25-dihydroxy-vitamin D3 in experimental sepsis. Int J Med Sci 2007, 4, 190-195.10.7150/ijms.4.190192515217657282
Search in Google Scholar
22. Pozo D., Guerrero J.M., Calvo J.R.: Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibit LPS-stimulated MIP-1α production and mRNA expression. Cytokine 2002, 18, 35-42.10.1006/cyto.2002.102412090758
Search in Google Scholar
23. Said S.I.: Vasoactive intestinal peptide and nitric oxide: divergent roles in relation to tissue injury. Ann NY Acad Sci 1996, 805, 379-387.10.1111/j.1749-6632.1996.tb17498.x8993418
Search in Google Scholar
24. Saito K., Yamatani K., Manaka H., Takahashi K., Tominaga M., Sasaki H.: Role of Ca2+ on vasoactive intestinal peptide-induced glucose and adenosine 3',5'- monophosphate production in the isolated perfused rat liver. Endocrinology 1992, 130, 2267-2273.10.1210/endo.130.4.1372240
Search in Google Scholar
25. Tuncel N., Tore F., Sahinturk V., Ak D, Tuncel M.: Vasoactive intestinal peptide inhibits degranulation and changes granular content of mast cells: a potential therapeutic strategy in controlling septic shock. Peptides 2000, 21, 81-89.10.1016/S0196-9781(99)00177-1
Search in Google Scholar
26. van Devender S.J.H., Buller H.R., ten Cate J.W., Aareden L.A., Hack C.E., Sturk A.: Experimental endotoxemia in humans; analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood 1990, 76, 2520-2526.
Search in Google Scholar
27. van Veen S.Q., Cheung C.W., Meijers J.C.M., van Gulik T.M., Boermeester M.A.: Anticoagulant and antiinflammatory effects after peritoneal lavage with antithrombin in experimental polymicrobial peritonitis. J Thromb Haemost 2006, 4, 2343-2351.10.1111/j.1538-7836.2006.02167.x16911675
Search in Google Scholar
28. van Westerloo D.J., Giebelen I.A.J., Meijers J.C.M., Daalhuisen J., de Vos A.F., Levi M., van der Poll T.: Vagus nerve stimulation inhibits activation of coagulation and fibrinolysis during endotoxemia in rats. J Thromb Haemost 2006, 4, 1997-2002.10.1111/j.1538-7836.2006.02112.x16805873
Search in Google Scholar
29. Yamazaki M., Aoshima K., Mizutani T., Ontachi Y., Saito M., Morishita E., Asakura H., Matsuda T., Triplett D.A.: Prednisolone inhibits endotoxin-induced disseminated intravascular coagulation and improves mortality in rats: İmportance of inflammatory cytokine suppression Blood Coag Fibrinol 1999, 10, 321-330.10.1097/00001721-199909000-0000210493213
Search in Google Scholar
30. Yang H., Li Q.W., Han Z.S., Hu J.H., Li W.Y., Liu Z.B.: Recombinant human antithrombin expressed in the milk of non-transgenic goats exhibits high efficiency on rat DIC model. J Thromb Thrombolysis 2009, 28, 449-457.10.1007/s11239-009-0347-x19455283
Search in Google Scholar
31. Yazar E., Col R., Konyalıoglu S., Birdane Y.O., Elmas M., Bas A.L.: Effects of vitamın E and prednisolone on biochemical and haematological parameters in endotoxaemic New Zealand white rabbits. Bull Vet Inst Pulawy, 2004, 48, 105-108.
Search in Google Scholar
32. Yun-Choi H.S., Pyo M.K., Chang K.C., Lee D.H.: The effects of higenamine on LPS-induced experimental disseminated intravascular coagulation (DIC) in rats. Planta Med 2002, 68, 326-329.10.1055/s-2002-2674111988856
Search in Google Scholar

Effect of Vasoactive Intestinal Peptide (VIP) on Cytokine Levels and Haemostatic and Biochemical Parameters in A Rat Endotoxaemic Model

Abstract

Paradigm

My account