Sepsis is a serious medical condition characterized by organ dysfunction resulting from the host's dysregulated response to infection. International epidemiological data indicate that the mortality rate of patients with sepsis exceeds that of myocardial infarction, making it the leading cause of non-cardiac deaths in the ICU(Mayr, Yende et al. 2014).
Among all patients with sepsis, older individuals are more susceptible to infections caused by gram-negative microorganisms. As such, the incidence of the disease is significantly higher in the elderly compared to younger individuals. A previous study conducted by Martin reported that adults over the age of 65 were 1.31 times more susceptible to acquiring a gram-negative infection in comparison to those under the age of 65. (Martin, Mannino et al. 2006) Additionally, elderly adults with infections frequently exhibit atypical symptoms, which can complicate the swift diagnosis and prompt initiation of treatment. Fever, a common clinical manifestation of infection and a frequently encountered sepsis-associated symptom is not present in roughly 30–50% of the elderly patients afflicted with infection(Ewig, Klapdor et al. 2012). Hence, early diagnosis and treatment of numerous elderly patients threatened by sepsis can be difficult to achieve.
Given this context, the identification of safe and effective prognostic biomarkers in elderly sepsis patients holds significant importance for clinicians. These advancements could aid in the development and implementation of timely and effective treatment strategies to reduce mortality rates among elderly sepsis patients. Many researchers concur that Procalcitonin (PCT) serves as a highly sensitive and specific biomarker for detecting severe bacterial infections. Thus, PCT measurements offer valuable insights into clinical scenarios where they are most beneficial(Hoeboer, van der Geest et al. 2015, Mihajlovic, Brkic et al. 2017). The present experimental results suggest (and confirm) that PCT is meaningful in predicting 28-day mortality in elderly patients with sepsis (P = 0.01). The AUC was determined to be 59.3%, with a sensitivity of 46.3% and specificity of 73.2%. These results generally align with the outcomes reported in previous related studies.
Moreover, regarding 28-day mortality, The results of the binary logistic regression analysis reveal that Lac and IL-8, together with the SOFA and APACHE II scores, acted as independent predictors, whereas PCT did not. The AUC of the SOFA score was 0.844, surpassing that of APACHE II (0.761), Lac (0.740), and IL-8 (0.751). Previous studies have already demonstrated the effectiveness of the SOFA scoring system in predicting mortality among adult sepsis patients(Raith, Udy et al. 2017). This consistency is reflected in the present results, where the SOFA score exhibited the highest prognostic value for elderly patients with sepsis.
The cytokine interleukin IL-8, known for its pro-inflammatory properties, is a key member of the chemokine family and plays a crucial role in the pathogenesis of sepsis. Numerous studies conducted over the years have shown that IL-8 can serve as a valuable biomarker for predicting infections and septic events. Kraft et al. confirmed that IL-8 demonstrates remarkable sensitivity and specificity as a biomarker for assessing burn size, particularly when its plasma concentration is below a threshold of 234 pg/ml. Moreover, at higher levels, plasma IL-8 concentration exhibits a strong correlation with the frequency of septic events. Moreover, IL-8 holds potential as a valuable biomarker for predicting infections and septic incidents in patients suffering from burn injuries(Kraft, Herndon et al. 2015).
In another experiment conducted by Liu XW, patients with IL-8 levels exceeding normal were found to be more susceptible to acute lung injury(Liu, Ma et al. 2019). Further, it has been suggested that the initial levels of IL-8 can be one of the most prognostic factors for mortality in sepsis patients(Zhou, Cheng et al. 2015). In a study by Wong et al.(Liou, Chang et al. 2014) involving pediatric patients with serum IL-8 levels of 220 pg/ml or lower obtained within 24 hours of admission, the data demonstrated the effectiveness of IL-8 in predicting a significant probability of survival in children with septic shock. Therefore, one may infer that IL-8 serves as a suitable stratification tool for interventional trials related to pediatric septic shock.
The present study aimed to verify the association between IL-8 levels and the prognosis of sepsis in elderly patients. In the experimental trials, findings were made that IL-8 in the non-survivor group was higher than in the survivor group [10.85(5.13,31.68) vs. 25.1(11.29-116.42), P = 0:00] and IL-8 emerged as a significant independent prognostic indicator for the 28-day mortality of elderly individuals, an outcome confirmed by logistic analysis [OR 1.011(1.005–1.017)), P = 0:001]. The sensitivity and specificity of IL-8 in predicting sepsis were 74.3% and 63.4% respectively, and the area under the ROC curve was 70.1%. Compared with the levels of blood lactic acid, there was no statistical significance (Z = 0.1337, P = 0.894) between IL-8 and lactic acid.
Various related studies have evaluated lactate as an effective prognostic indicator for assessing sepsis patients(Gattinoni, Vasques et al. 2019, Grealish, Chiew et al. 2021). For instance, Grealish et al. investigated lactate values in critically ill patients admitted to the Emergency Department with or without diabetes and conducted a multivariable analysis with this patient sample. Their results demonstrated that lactate remained an independent predictor of ICU/in-hospital mortality in the non-diabetes group(Gattinoni, Vasques et al. 2019). In the present study, the sensitivity of IL-8 was 74.5%, while the cut-off value of IL-8 was 14.497pg/ml, nearly 76.5% for LAC. The specificity of IL-8 was 63.4%, which was slightly higher than that of lactic acid (56.3%). Both IL-8 and LAC were found to be independent risk factors for the prognosis of elderly patients with sepsis. Comparing their AUCs (Z = 0.134, P = 0.894), no statistically significant differences were found in the AUC values for IL-8 and LAC. Additionally, sensitivity and specificity analyses showed similar diagnostic value between IL-8 and LAC. In some respects, IL-8 may even be considered superior to lactate.
The AUC of IL-8 in combination with the SOFA score was significantly higher when compared to that of IL-8 alone (Z = 3.454, P = 0.005). The AUC of IL-8 in combination with the SOFA score was slightly higher than that of SOFA (Z = 0.463, P = 0.644). The SOFA score was proposed by the European Society of Intensive Care Medicine (ESICM) in 1994 (Vincent, Moreno et al. 1996) and has since been associated with mortality rates in sepsis patients(Ferreira, Bota et al. 2001, Park, Lee et al. 2023). At present, it is widely utilized to assess the severity of sepsis and to perform prognostic evaluations(Oh, Roh et al. 2020). The present results are consistent with these claims and indicate that SOFA scores have the highest predictive value for sepsis patients. Compared with the SOFA score, the APACHE II score also demonstrated a high predictive value for 28-day mortality. While no single prediction biomarker stood out prominently, their predictive value increased significantly when combined with other prognostic indicators.
Further findings were made that the utilization of plasma IL8 thresholds consistently aided in the identification of individuals at an elevated risk of mortality among elderly patients with sepsis. The results demonstrate that IL-8 could potentially serve as a prognostic factor for sepsis trials. After integrating it with the SOFA and APACHE II scoring systems, the prognostic value of IL-8 was significantly enhanced, providing valuable guidance for the clinical management and prognosis of sepsis. Utilizing these markers in the analysis of high-risk elderly patients could improve the efficacy and robustness of clinical trials while reducing the number of sepsis patients exposed to potentially harmful treatments unnecessarily.
In the present literature review, several studies on IL-8 and its relationship with the prognosis of elderly patients with sepsis were discerned. The present study represents a pioneering effort in this field, and the conclusions hold significant importance for both the scholarly and medical communities. In future studies, the aim will be to further explore the risk stratification and predictive efficacy of IL-8 in the context of elderly septic patients to enhance the value of the present findings.
Nonetheless, the present research has several limitations. First, the present study was limited to a single center and had a relatively small sample size. As such, large-scale, multi-center studies are needed to verify the results.
Second, the dynamic correlation between IL-8 fluctuations and the prognosis of elderly sepsis was not actively monitored, necessitating further exploration in future studies.
Lastly, while initial serological markers provide insight into the inflammatory response and disease severity at the disease's onset, they have limitations in predicting the ultimate prognosis comprehensively.