Etanolün uygulanma dozu ve süresine bağlı olarak alkolik gebelerde immün sistem değişimleri

Sağlıklı gebelik maternal immünsupresyonu ve immun tolerans gelişimini zorunlu kılar. Gebelik sürecinde annede geliştirilen immünolojik tanıma reaksiyonlarının farklılığı, bu süreçte immün sisteme özgün yeni bir dengenin oluşmasını sağlar. Gebelikte fetusun gelişimi sırasında kullanılan teratojenik faktörlerin oluşturacağı malformasyonların immün sistemi nasıl etkilediği cevaplanmamış bir sorudur. Araştırmamız, sağlıklı ve gebe gruplarında farklı sürelerde ve dozlarda alınan alkolün annede immün sisteme etkisini belirlemek amacıyla planlanmıştır. Çalışmamızda 10-12 haftalık a/a Wistar albino soyu dişi sıçanlar kullanıldı. Sıçanlar; Kontrol grubu (C), %17.5 etanol uygulanan grup (E), %30 gavaj etanol uygulanan grup (GE), Kontrol gebe grubu (CG), %17.5 diyet etanol uygulanan gebe grubu ve %30 gavaj etanol uygulanan gebe grubu olmak üzere 6 grup (n=60) oluşturuldu. Diyet etanol uygulanan gruba 4 ay boyunca günde 8.75 g/kg., gelecek şekilde %17.5 diyet etanol, gavaj yöntemi uygulanacak gruba ise 2 ay boyunca günde 6 g/kg., gelecek şekilde %30 etanol uygulandı. Bu uygulamanın ardından gebe bırakıldılar ve alkol uygulamasına devam edildi. Alınan kan örneklerinde CD4, CD8, CD19 analizi; Flow sitometrik yöntemle, IL-1 ve IL-2 düzeyi; Elisa yöntemiyle tayin edildi. Araştırmamızda (C) ile (E) grubu karşılaştırıldığında, (C) grubuna göre, CD4, CD3, IL-1 düzeyindeki anlamlı artışa karşın, CD8, CD19, IL-2 düzeyindeki azalmayla immün supresyon belirlendi. (C) ile (GE) grubu karsılaştırıldığında, (C) grubuna göre, CD4, CD3, CD19 ve IL- 1 düzeyinde değişim gözlenmezken, gebeliğin kilit sitokini olan IL-2 düzeyindeki azalma, CD8 azalmasının temel nedeni olarak belirlendi. (CG) ile (EG) gruplarının karşılaştırılmasında, (CG) ye göre, CD4, CD8, CD19 ve IL-2 düzeylerinde azalmayla gelişen immun supresyonu görürken, CD3 ve IL-1 düzeylerinde artış saptandı. (CG) ile (GEG) karşılaştırıldığında ise, (CG) ye göre, CD4, CD3 düzeyinin değişmediği, CD8, CD19, IL-2 düzeylerinde azalma olduğu, IL-1 düzeyinde ise artışın olduğu belirlendi. Çalışma grupları kendi aralarında karşılaştırıldığında, (C) ile (CG) arasında, (C) grubuna göre CD4 (%18), CD3 (%19), IL-2 (%24) oranında azalırken, CD8 (%8), CD19 (%7) değişim gözlenmemiş, IL-1 (%28) ise artmıştır. (E) ve (EG) gruplarında ise (E) grubuna göre, CD4 (%46), CD8 (%20), CD3 (%22), CD19 (%31), IL-1 (%34) artış göstermiştir. (GE) ve (GEG) gruplarına baktığımızda ise, (GE) ye göre CD4 (%24), CD8 (%13), CD3 (%24), CD19 (%23), IL-2 (%15) azalmış, buna karşın IL-1 (%29) oranında artmıştır. Gruplar arasında en anlamlı değişim, uzun süreli diyet etanol uygulanan grupta gözlendi. Sonuç olarak; direkt ve indirekt etanol uygulanan gebe sıçanlarda spesifik immun parametrelerde güçlü bir immunsupresyonun olduğu, etanolün uygulama süresi ve yönteminin supresyon kuvvetini etkilediği gözlendi.

Effect of dose and duration of ethanol administration on the immune system in pregnancy

Background and Design.- Maternal immunosuppression and immunotolerance are required during a successful pregnancy. Differential regulation of the immune system by the maternal immune system enables this interaction during pregnancy. Effect of teratogenic substances used during fetal development on the maternal immune status is not fully understood. Our purpose was to study the role of alcohol on the maternal immune system following a variety of doses and administration routes. Wistar albino rats (10-12 weeks of age) were used in this study. Six experimental groups (n=10 each) consisted of controls (C), control pregnant (CG); those who received 17.5% ethanol by diet (E), and their pregnant counterparts (EG), and the 30% gavage ethanol group (GE) and pregnant rats treated similarly (GEG). Group administered ethanol by diet was treated for 4 months (8.75 g/kg/day); and gavage was treated for 2 months (6 g/kg/day). Subsequently these rats were impregnated, and ethanol treatments were continued. Lymphocytes were analyzed by flow cytometry for CD3, CD4, CD8 and CD19. IL-1 and IL-2 levels were determined by ELISA. Results.- Ethanol treated group demonstrated significant increase in CD4, CD3 and IL-1 compared to the control group. Same group demonstrated decrease in CD8, CD19 and IL-2. In the gavage group there was no change in CD4, CD3, CD19 and IL-1, however IL-2 and CD8 were decreased compared to controls. In the pregnant groups there was decrease in CD4, CD8, CD19 and IL-2 in the EG group compared to control pregnant rats, and CD3 and IL-1 were increased. Comparison of the GEG to CG showed that there was no change in CD4 and CD3, decrease in CD8, CD19 and IL-2, and increase in IL-1. When experimental groups were compared to controls, there was decrease in CD4 (18%), CD3 (19%), IL-2 (24%) in the control pregnant group compared to controls. There was no change in CD8 and CD19, however IL-1 (28%) was increased. When ethanol treated pregnant group was compared to ethanol group, significant increases in CD4 (%46), CD8 (%20), CD3 (%22), CD19 (%31) and IL-1 (%34) were seen. In the pregnant gavage group decrease in CD4 (%24), CD8 (%13), CD3 (%24), CD19 (%23), and IL-2 (%15), and %29 increase in IL-1 was demonstrated compared to non-pregnant gavage group. Most significant changes were observed in the long-term ethanol treated group. Conclusion.- Our results demonstrate that ethanol administration resulted in variable amount of immunosuppression in pregnant rats depending on the duration and method of administration.

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