Predrag Romic

Polymorphisms of genes encoding tumor necrosis factor-alpha, interleukin-10, cluster of differentiation-14 and interleukin-1ra in critically ill patients

PURPOSE The aim of the study was to determine whether distributions of tumor necrosis factor (TNF)-α(308), interleukin (IL)-10(1082), CD14(159), and IL-1ra gene intron 2 genotypes in critically ill patients are associated with outcome, underlying cause of sepsis, and type of microorganism. MATERIALS AND METHODS Blood samples from 106 critically ill white patients were genotyped by method based on polymerase chain reaction for TNF-α(308), IL-10(1082), CD14(159), and IL-1ra gene intron 2. RESULTS All patients with TNF-α(308)AA genotype survived; relative risk (RR) of death in patients with AG was 3.250 and with GG, 1.923 (P < .01). In patients with Gram-positive sepsis, IL-10(1082)AA and then AG genotypes were the most frequent ones (odds ratio [OR], 18.67 and 7.20, respectively; P < .01). When comparing IL-10(1082)AA with AG, RR of pancreatitis was 1.80 and OR was 3.40. When AA and GG were compared, RR was 7.33 and OR was 20.00. In patients with GG, RR of peritonitis was 4.07 and OR was 5.88 (P < .01). In patients with Gram-positive sepsis, CD14(159)CT was the most frequent one with OR of 5.25. Distribution of 6 IL-1ra gene intron 2 genotypes showed no significant association. CONCLUSIONS Distribution of TNF-α(308) genotypes is associated with outcome, IL-10(1082) with type of microorganism and underlying cause of sepsis, and CD14(159) with type of microorganism.

New aspects of sepsis pathophysiology in critically ill

Jos od doba Hipokrata koji je 400. godine pne prvi opisao sepsu, imunopatofiziologija ovog kompleksnog oboljenja ostaje kontroverzna tema koja je predmet mnogih istraživanja. I autori ovog opsteg pregleda posvetili su se u poslednjoj dekadi ovoj intrigantnoj oblasti i to sa razlictitih aspekata. Naime, proucavali smo disfunkciju razlicitih organa u sepsi (miokarda i pluca), kao i sindrom multiple organske disfunkcije (MODS), zatim imunsku kaskadu sepse i ulogu proi antiinflamatornih citokina, odnos infekcije i inflamacije, acidobazni status bolesnika sa sepsom i genski polimorfizam kod razlicitih medijatora i receptora od znacaja za težinu i ishod sepse . Svojim istraživanjima u protekllih 10 godina obuhvatili smo veoma veliki broj bolesnika sa traumom i ratnom povredom koje su se veoma cesto komplikovale sekundarnom sepsom, kao i sepsom druge etiologije a, takođe, ispitivali smo i skorove sepse kod razlicitih bolesnika.