Effects of conivaptan and mannitol on serum cytokine levels (TNF-α, IL-15 and IL-35) following bilateral carotid artery occlusion

Year 2018, Volume: 1 Issue: 1, 22 - 28, 15.08.2018

Betül Can , Semih Öz , Ahmet Musmul Tuğba Erkmen Ezgi Yaver Meltem Erdaş Özkan Alataş

Abstract

This study was aimed to investigate the post-ischemic effects of
aquaretic conivaptan and diuretic mannitol on serum tumor necrosis factor-α
(TNF-α), interleukin-15 (IL-15) and interleukin-35 (IL-35) levels in an
experimental cerebral ischemia-reperfusion (I/R) rat model. Healty male
Sprague-Dawley rats were randomly divided into five groups: Control (Sham), I/R
(I/R+Saline), MAN (I/R+mannitol), CON10 (I/R+conivaptan 10 mg/ml), and CON20
(I/R+conivaptan 20 mg/ml). Cerebral ischemia was conducted using bilateral common
carotid artery occlusion technique. At the onset of reperfusion, saline,
conivaptan or mannitol were administrated intravenously. The blood samples were
taken at 6th hours of reperfusion. Rat serum TNF-α, IL-15 and IL-35 levels were
measured by using commercial ELISA Kits. The biochemical analyses showed that
I/R method led to an increase in serum TNF-α and IL-15 levels when compared
with the control. Conivaptan treatments decreased TNF-α and IL-15 levels
significantly compared to the I/R group (p<0.001). IL-35 levels were high in
all ischemia groups, but 10 mg/ml conivaptan brought its levels close to the
control (p<0.001). The results of Spearman’s correlation analyses showed
that serum TNF-α levels were positively correlated with IL-15 levels (p<0.001,
r=0.596) and IL-35 levels (p<0.05, r=0.319). According to our findings on
pro-inflammatory and anti-inflammatory cytokine levels, conivaptan was
dose-dependently more effective than mannitol in balancing inflammatory
response. This study may provide useful information in the development of
treatment/follow-up strategies for ischemia and inflammation related diseases
such as stroke and brain edema.

Keywords

brain edema, conivaptan, interleukin, mannitol, serum cytokines

Bilateral Karotis Arter Oklüzyonu Sonrasında Conivaptan ve Mannitol’ün Serum Sitokin (TNF-α, IL-15 ve IL-35) Düzeyleri Üzerine Etkileri

Abstract

Bu çalışmada, deneysel serebral iskemi-reperfüzyon
hayvan modelinde akuaretik Conivaptan ve diüretik Mannitol tedavilerinin serum
tümör nekroz faktör-α
(TNF-α), interlökin-15 (IL-15)
ve interlökin-35 (IL-35)
düzeylerine post-iskemik etkilerinin araştırılması amaçlanmıştır. Sağlıklı
erkek Sprague-Dawley sıçanlar rastgele 5 gruba ayrılmıştır: Kontrol
(Sham), I/R (I/R+Salin), MAN (I/R+Mannitol), CON10 (I/R+Conivaptan 10 mg/ml),
and CON20 (I/R+Conivaptan 20 mg/ml). Serebral iskemi, bilateral kommon karotis
arter oklüzyonu tekniği kullanılarak gerçekleştirilmiştir. Reperfüzyonun
başlangıcında salin, conivaptan veya mannitol intravenöz yolla uygulanmıştır.
Kan örnekleri reperfüzyonun 6. saatinde alınmıştır. Sıçan TNF-α, IL-15 ve IL-35 serum düzeyleri
ticari ELISA kitleri kullanılarak ölçülmüştür. Biyokimyasal analizler, I/R
uygulamasının TNF-α ve IL-15 düzeylerinde
kontrole göre artışa yol açtığını göstermiştir. Conivaptan tedavileri TNF-α ve IL-15
düzeylerini I/R grubuna göre anlamlı düzeyde azaltmıştır (p<0.001).
IL-35 düzeyleri tüm iskemi gruplarında yüksek bulunurken, 10 mg/ml Conivaptan
tedavisi IL-35 düzeylerini kontrol grubu düzeylerine yaklaştırmıştır (p<0.001).
Yapılan Spearman korelasyon analizleri, serum TNF-α düzeylerinin IL-15
(p<0.001, r=0.596) ve IL-35 (p<0.05, r=0.319) düzeyleri ile pozitif yönde
ilişkili olduğunu göstermiştir. Sonuç olarak pro-inflamatuar ve anti-inflamatuar
bu sitokin düzeylerine dair bulgularımız, Conivaptan’ın doza bağlı olarak inflamatuar
yanıtın dengelenmesinde Mannitol’den daha etkili olduğunu göstermektedir. Bu
çalışma, inme ve beyin ödemi gibi iskemi ve inflamasyon ile ilişkili
hastalıkların tedavi ve takibine yönelik stratejilerin geliştirilmesinde
yararlı bilgiler sağlayabilir.

Keywords

beyin ödemi, conivaptan, interlökin, mannitol, serum sitokinleri

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