The term sepsis is used to define the systemic inflammatory response to an infectious agent (i.e., bacterial, viral, fungal, or parasitic). Despite the use of new treatment modalities, improvement in technology, and increased experience, the sepsis mortality rate remains high (Schrag et al, 2012). Sepsis continues to be a disease with high fatality, and efforts are directed toward early diagnosis and treatment (Naffaa et al, 2013).
Identification of sepsis in patients with fever and other clinical symptoms and signs is crucial for timely implementation of antimicrobial treatment and predicting prognosis. Diagnosis of sepsis is difficult because the signs and symptoms of sepsis overlap with those of viral infections.It is also hard to diagnose as it may be obscured by noninfectious causes of SIRS. In addition, culture-negative bacterial infection hinders the diagnosis of sepsis. Microbiologic methods as well as identification of biomarkers and molecular markers have been explored as strategies for detecting sepsis (Jekarl et al, 2013).
We aimed to determine the diagnostic and prognostic values of serum level of both total IL6 and IL6-174 different genotypes (G/G, G/C and C/C) in critically ill pediatric patients with various grades of sepsis admitted to the ICU.
The study included 30 patients with various grades of sepsis and 30 healthy controls of matching age for comparison. Patients were subjected to full history, physical examination, routine laboratory and radiological investigations were done as needed. Special blood samples (5 ml) had been withdrawn from both patients and control.2 ml. of them were collected on EDTA for DNA extraction and RFLP of IL-6 gene at 174. The rest was used for separation of serum for determination of IL-6 protein by ELISA technique.
We had found that total serum level of IL6 was high in cases in comparison to control, which means that there is positive correlation between high level of IL6 and sepsis. There was positive correlation between high level of IL6 and high level of CRP. There was also insignificant correlation between the level of IL6 and the level of IL6-174G/C promoter polymorphisms. Another insignificant correlation was between IL6 and age of the patients and with maximum body temperature. Regarding IL6 level in diagnosis of sepsis, cut off value= 5.5 micg/dl and AUC=0.87, IL6 is considered good positive than negative diagnostic factor. Regarding IL6 in prediction of sepsis outcome, cut off was 30 micg/dl and AUC =0.50, so IL6 can’t predict sepsis mortality.
Considering IL6-174 different genotypes, we found that G/C found in 53.3% of the cases, G/G found in 36.7%, and C/C in only 10%. Most of the G/C patients had leucocytosis and bandemia, but protected from poor sepsis complications like metabolic acidosis, anemia, coagulation defect, elevated liver and kidney functions, hypotension or DIC. On the other hand many of the G/G patients suffered from these complications while most of the C/C did.
Regarding sepsis outcome 53.3% of G/C patients improved and discharged, 33.3% of G/G improved while 100% of C/C died.
Conclusion:
Collectively, our data supported the possibility of the presence of the IL6-174 G/C SNP that may account for individual differences in the severity and outcome of sepsis. We observed an association between heterozygosity for IL6-174 G/C and a protection against severe sepsis complications and hospital mortality. So we can use serum level of total IL6 for diagnosis of sepsis while IL6 different genotypes for prediction of sepsis outcome.