Gebeliğin farklı evrelerinde NK (CD56) ve IFN-γ etkileşimi üzerine farklı dozlardaki alkolün etkisi

Amaç: Gebelikte maternal reddin egellenmesi, immün toleransın gelişmesi inhibitör veya stimülatör faktörlerin etkisiyle olmaktadır. Gebeliğin devamı, immünsupresyon ile sağlanmaktadır. Bu sureçte teratojenik faktörler direkt fetusu etkileyerek tolerans mekanizmasını değiştirmektedir. Araştırmamızda, gebeliğin farklı evrelerinde, farklı dozda alkolün hem doğal hem de spesifik immün sistemin kilit hücreleri olan NK(CD56) ve sitokinleri ile etkileşimini incelemeyi planladık. Yöntem: Çalışmamızda 60 wistar albino soyu dişi sıçanla 6 çalışma grubu oluşturuldu. (Kontrol grubu, %17.5 diyet etanol uygulanan grup, %30 gavaj etanol uygulanan grup, kontrol gebe, %17.5 diyet etanol uygulanan gebe, %30 gavaj etanol uygulanan gebe). NK (CD56); Antikandidal İndeks Tayin Metodu, CD19, IL-2r (CD25), Flow Sitometrik Yöntemiyle ve IL-1, IL-2, IFN-g, ELISA yöntemiyle tayin edildi.Bulgular: Bulgularımızda gebeliğin 3. evresinde (17. gün) özellikle gavaj etanol uygulanan gruplarda güçlü supresyonun olduğunu gösterdik.Sonuç: Sonuç olarak, direkt ve indirekt uyguladığımız etanolün supressif etkisinin gebeliğin ileri evresinde güçlü olduğu ve uygulanan alkolün bu dozların kritik seviyelerde olduğunu bulduk. Daha yüksek dozda alkolün abortus riskini arttıracağını ve fetal anomaliyi arttıracağı yönünde bulgular bu düşünceyi güçlendirmektedir.

The interaction of alcohol at various doses with NK and IFN-gamma at each pregnancy stage

Objectives: During pregnancy, the factors affecting maternal rejection are immune tolerance development inhibitors or stimulators. Pregnancy progresses as a result of immunosuppression. Teratogenic factors which directly affect the fetus alter tolerance mechanisms. This study examined the interaction effect of alcohol at different dose rates with both natural and specific lock NK(CD56) and cytokines at various stages of pregnancy.Methods: In this study 60 female Wistar albino rats were randomly assigned to 6 groups: For non pregnant and pregnant rats there were three groups (a) controls, (b) control pregnant (c) alcohol 17.5% of diet, (d)pregnant rats treated similarly (e) alcohol 30% by gavage (f) pregnant group received ethanol through gavage NK(CD56) levels were determined by the Anticandidal Index Determination Method, CD 19 and IL-2r(CD25) by the Flow Cytometric Method and IL-1, IL-2 and IFN-g; by the ELISA method.Results: Suppression at (the advanced stage of pregrancy) stage 3 (17 days) in the both alcohol groups was markedly higher than controls and suppression in the 30% alcohol group significantly higher than in the 17.5% group.Conclusion: This is supported by findings that higher doses of alcohol increase the risk of abortion and fetal abnormalities.

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  • 1. Akyol S, Tunalı H. Alkolik yapılan gebe sıçanlar ve yavrularında NK aktivasyonu ile IL-2, IFN-g ve CD19 etkileşimi. Cerrahpaşa Tıp Derg 2001; 32: 43-50.
  • 2. Akyol S, Tunalı H. Etanolün uygulanma dozu ve süresine bağlı olarak alkolik gebelerde immün sistem değişimleri. Cerrahpaşa Tıp Derg 2005; 36: 181-223.
  • 3. Plackett TP, Kovacs EJ. Acute models of ethanol exposure to mice. Methods Mol Biol 2008; 447: 3-9.
  • 4. Coleman RA, Young BM, Turner LE, Cook RT. A practical method of chronic ethanol administration in mice. Methods Mol Biol 2008; 44: 49-59
  • 5. Vacchio MS, Jiang SP. The fetus and the maternal immune system: pregnancy as a model to study peripheral T-cell tolerance. Crit Rev Immunol 1998; 15: 2677-2683.
  • 6. Jiang SP, Vacchio MS. Multiple mechanisms of peripheral T cell tolerance to the fetal "allograft". J Immunol 1998; 160: 3086-3090.
  • 7. Mincheva-Nılsson L. Pregnancy and gama/delta T cells: Taking on the hard question. Reproductive Biology and Endocrinology 2003; 1: 120-125.
  • 8. Shi YY, Ling B, Zhou Y, Gao T, Feng DQ, Xiao M, Feng L. Innate immune defences in the human uterus during pregnancy. Placenta 2007; 28: 1099-1106.
  • 9- Wasowka BA, Lee CY, Halushka MK, Baldwin WM 3r. New concepts of complement in allorecognition and graft rejection. Cell Immunol 2007; 248: 18-30.
  • 10. Koch CA, Platt JL. T cell recognition and graft rejection. Cell Immunol 2007; 248: 18-30.
  • 11. La Rosa DF, Rahman AH, Turka LA.The innate immune system in allograft rejection and tolerance.J Immunol 2007; 15: 7503-7509.
  • 12. Wolcott RM, Jennings SR, Chervenak R. Effects of in utero alcohol exposure on B-cell development in the murine fetal liver. Alcohol Clin Exp Res 1995; 19: 170-176.
  • 13. Szabo G, Klenk G, Veer A. Effects of in utero alcohol exposure on B-cell development in the murine fetal liver. Alcohol Clin Exp Res 1998; 22: 1706-1712.
  • 14. Szabo G, Klenk G, Veer A. Correlation between the combination of alcohol consumption and smoking in oral cancer (screening of the population at risk) Orv Hetil 1997; 28: 3297-3299.
  • 15. Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 2004; 5: 266–271.
  • 16. Laird SM, Tuckerman EM, Cork BA, Linjawi S, Blakemore Al, Li TC. A review of immune cells and molecules in women with recurrent miscarriage. Hum Reprod Update 2003; 9: 163-174.
  • 17. Jerrells TR, Weinberg J. Influence of ethanol consumption on immune competence of adult animals exposed to ethanol in utero. Alcohol Clin Exp Res 1998; 22: 391-400.
  • 18. Jerrells TR, Eckardt MJ, Weinberg J. Mechanisms of ethanol-induced immunosuppression. Prog Clin Exp Res 1990; 325: 173-180.
  • 19. Chang MP, Wang Q, Norman DC. Diminished proliferation of B blast cell in response to cytokines in ethanol-consuming mice. Immunopharmacol Immunotoxicol 2002; 24: 69-82.
  • 20. Coleman RA, Young BM, Turner LE, Cook RT. A practical method of chronic ethanol administration in mice. Methods Mol Biol 2008; 447: 49-59.
  • 21. Jeannet G, Coudert JD, Held W. T and B lymphocytes exert distinct effects on the homeostasis of NK cells. Eur J Immunol 2006; 36: 2725-2734.
  • 22. Taylor AN, Tio DL, Chiappeli F. Thymocyte development in male fetal alcohol-exposed rats. Alcohol Clin Exp Res 1999; 23: 465-470.
  • 23. Zhou J, Zhang J, Lichtenheld MG, Meadows GG. A role for NF-kappa B activation in perforin expression of NK cells upon IL-2 receptor signaling.J Immunol 2002; 1: 1319-25.
  • 24. Zhou J, Meadows GG. Alcohol consumption decreases IL-2-induced NF-kappaB activity in enriched NK cells from C57BL/6 mice. Toxicol Sci 2003; 73: 72-79.
  • 25. Wu WJ, Wolcot RM, Pruett SB. Ethanol decreases the number and activity of splenic natural killer cells in a mouse model for binge drinking. J Pharmacol Exp Ther 1994; 271: 722-729.
  • 26. Saito S, Shima T, Nakashima A, Shiozaki A, Ito M, Sasaki Y. What is the role of regulatory T cells in the success of implantation and early pregnancy? J Assist Reprod Genet 2007; 24: 379-386.
  • 27. Arjona A, Sarkar DK. Are Circadian Rhythms the Code of Hypothalamic-Immune Communication? Insights from Natural Killer Cells. Neurochem Res 2007; 33: 708-718.
  • 28. Arjona A, Boyadjieva N, Kuhn P, Sarkar DK. Changes in immune activation markers during pregnancy and postpartum. J Reprod Immunol 1999;42: 147-165.
  • 29. Burns DN, Nourjah P, Wright DJ, Minkoff H, Landesman S, Rubinstein A, Goedert JJ, Nugent RP. Changes in immune activation markers during pregnancy and postpartum. J Reprod Immunol 1999; 42: 147-165.
  • 30. Chang MP, Yamaguchi DT, Yeh M, Taylor AN, Norman DC. Mechanism of the impaired T-cell proliferation in adult rats exposed to alcohol in utero. Int J Immunopharmacol 1994; 16: 345-357.
  • 31. Burchill MA, Yang J, Vang KB, Farrar MA. Interleukin-2 receptor signaling in regulatory T cell development and homeostasis. Immunol Lett 2007; 114: 1-8.
  • 32. Zhang X, Sliwowska JH, Weinberg J. Chronic ethanol consumption by mice results in activated splenic T cells. J Leukoc Biol 2002; 72: 1109-16.
  • 33. Taylor AN, Ben-Eliyahu S, Yirmiya R, Chang MP, Norman DC, Chiappelli F. Actions of alcohol on immunity and neoplasia in fetal alcohol exposed and adult rats. Alcohol Alcohol Suppl 1993; 2:69-74.
  • 34. Zhang X, Sliwowska JH, Weinberg J. Prenatal alcohol exposure and fetal programming: effects on neuroendocrine and immune function. Exp Biol Med 2005; 230: 376-388.
  • 35. Chang MP, Norman DC. Mechanism of ethanol-mediated immunosuppression in mice: ethanol suppresses T-cell proliferation without affecting IL2 production and IL2 receptor expression. Int J Immunopharmacol 1992; 14: 707-719.