Effects of different anesthetic agents on GM-CSF, MCP1, IL1α and TNFα levels in rat sepsis model

Abstract

Anesthetic agents could alter the course and outcome of physical trauma, as well as experimentally or naturally occuring severe infections, by regulating several immune response mechanisms. The aim of our study was to investigate the influence of several commercially used anesthetic agents (ketamine, propofole, pentylentetrazole - PTZ) on cytokine concentrations, animal survival and pathohistological changes in the model of rat sepsis. In adult, male Wistar rats after different anesthetic traeatment and induction of sepsis by cecal ligation and punction we estimated serum levels of IL1α, TNFα, GM-CSF and MCP-1 at 12h intervals. After 48h of sepsis induction, the largest number of animals survived in the group treated with PTZ (47%), while the lowest survival rate was in the propofole treatment group (24%). Contrary to survival rate, the most abundant pathohistological changes were seen on preparations from PTZ and than in ketamine/PTZ treated groups, without any significant changes in the CNS of propofole treated animals. In the propofole treated group there was a prominent increament of GM-CSF values at 12h and 24h, followed by a significant decreament at 36h. These changes were negatively correlated to the survival rate in this group. This group had the lowest levels of MCP1 at all evaluated time intervals. After high initial levels, IL1α and TNFα levels fell to undetectable concentrations and at 24h increased to a high level. In PTZ as well as ketamine groups, at 12 h interval, GM-CSF levels were lower than in the propofole treated group. Contrary, MCP-1 levels were higher in these groups comparing to propofole group. After a high initial peak, IL1α levels decreased to low but detectable levels, followed by an intensive rise in ketamine treated, but with further decrement in pentazole treated groups. TNFα levels were low through all evaluated intervals in both these groups. Our results indicate that induction of anaesthesia of animals with sepsis with variuos anesthetic agents is connected to different pathohistological CNS changes, distinct serum cytokine profiles and diverse survival rates.

Anestetici mogu izmeniti tok i ishod uticaja fizičke traume kao i eksperimentalno ili prirodno nastalih teških infekcija, regulacijom nekoliko mehanizama imunskog odgovora. Cilj naše studije je bio da ispitamo uticaj nekoliko komercijalno korišćenih anestetika (ketamina, propofola i pentzlentetrazola) na koncentraciju citokina, preživljavanje životinja i patohistološke promene u modelu sepse indukovane u pacova. U odraslih pacova, muškog pola, po primeni različitih anestetika i indukcije sepse podvezivanjem i punkcijom cekuma, utvrđivali smo nivoe IL1α, TNFα, IL4, IFNy, GM-CSF i MCp-1 u intervalima od 12 sati. Nakon 48 sati od indukcije sepse, najveći broj životinja preživeo je u grupi tretiranoj pentylenetetrazolom (50%), potom u ketamin/pentylenetetrazol tretiranoj grupi, dok je najmanja stopa preživljavanja bila u grupi tretiranoj propofolom (22%). Nasuprot stopi preživljavanja, najizraženije patohistološke promene su utvrđene na preparatima grupa tratiranih pentazolom i ketamin/pentylenetetrazol, bez značajnih promena u CNS u grupi životinja tretiranih propofolom. U uzorcima grupe tretirane propofolom detektovali smo intezivan porast vrednosti GM-CSF 12h i 24h, praćen značajnim padom posle 36h. Ove promene su negativno korelirale sa stopom preživljavanja u ovoj grupi. Ova grupa je imala i najniže vrednosti MCP-1 u svim praćenim vremenskim intervalima. Posle visokih inicijalnih nivoa, vrednosti IL1a i TNFα pale su na nedetektabilne a u terminu od 24h porasle su na visok nivo. U grupama tretiranim pentazolom i ketaminom, 12. sata, vrednosti GM-CSF bile su niže od grupe tretirane propofolom. Nasuprot tome, vrednosti MCP-1 su bile veće u ovim grupama u odnosu na propofolom tretiranu grupu. Posle visokog inicijalnog skoka, vrednosti IL1α smanjuju se na niske ali detektabilne vrednosti, a zatim sledi intezivan rast u ketaminom tretiranoj grupi i dalji pad vrednosti u pentilenetetrazol tretiranoj grupi. Vrednosti TNFα su u ove dve grupe bile niske u svim ispitivanim intervalima. Vrednosti IL4 i IFNy su bile praktično nedetektabilne u svim ispitivanim grupama. Naši rezultati ukazuju da je indukcija anestezije u životinja sa sepsom različitim anesteticima povezana sa različitim patohistološkim nalazima u CNS, različitim serumskim profilom citokina i različitom stopom preživljavanja.