Possible cytokine biomarkers in pediatric acute appendicitis

Abstract

Background: Diagnosis of acute appendicitis (AA) and decisions about its treatment remain among the most common dilemmas of pediatric surgical teams. Monitoring of immune response may be of importance for this purpose. Our aim was to measure and analyze serum and peritoneal fluid cytokines, in children who had undergone surgery for suspected AA.

Methods: Prospective investigation of serum and peritoneal fluid cytokine values was performed in 127 consecutive patients. According to the pathohistological findings, patients were divided into three groups: normal/early, uncomplicated and complicated AA. Determination of cytokine concentrations for 20 different cytokines was done using a commercial flow cytometry kit: Human Inflammation 20 plex BMS 819.

Results: Statistically significant differences in serum cytokine values between pathohistological groups were found for IP-10, MIP-1α and IL-10. Preoperative cut-off values of IP-10, MIP-1α and IL-10 between groups were obtained using ROC curve analysis. Positive correlations between serum and peritoneal concentrations were recorded for most of the analyzed cytokines.

Conclusion: IP-10, MIP-1α and IL-10 showed potential in assessment of AA in children. Confirmatory studies with a larger number of patients are required to prove reliability of these biomarkers.

Keywords: Acute appendicitis; Biomarker; Children; Cytokine.

Fig. 1

Preoperative comparison of serum cytokine values between pathohistological groups: IP-10 (a); MIP-1α (b); IL-10 (c). NEAA – normal or early acute appendicitis; UAA – uncomplicated acute appendicitis; CAA – complicated acute appendicitis. [mean ± standard error of mean (SEM), Mann-Withney test, *p < 0.05, **p < 0.01, ***p < 0.001]

Fig. 2

ROC (Receiver Operating Characteristic) curves of cytokines for formed pathohistological groups. NEAA – normal or early acute appendicitis; UAA – uncomplicated acute appendicitis; CAA – complicated acute appendicitis; IAA – inflamed acute appendicitis. ROC curve of IP-10 for NEAA and UAA (a); ROC curve IP-10 for NEAA and CAA (b); ROC curve of IP-10 for NEAA and IAA (UAA + CAA) (c); ROC curve of MIP-1α for UAA and CAA (d); ROC curve of IL-10 for UAA and CAA (e)

Fig. 3

Comparison of IP-10 values between pathohistological groups on the first postoperative day. NEAA – normal or early acute appendicitis; UAA – uncomplicated acute appendicitis; CAA – complicated acute appendicitis. [mean ± standard error of mean (SEM), Mann-Withney test, *p < 0.05, **p < 0.01, ***p < 0.001]

Fig. 4

Comparison of cytokine values between pathohistological groups on the third postoperative day: IL-10 (a); MIP-1α (b). NEAA – normal or early acute appendicitis; UAA – uncomplicated acute appendicitis; CAA – complicated acute appendicitis. [mean ± standard error of mean (SEM), Mann-Withney test, *p < 0.05, **p < 0.01, ***p < 0.001]

Fig. 5

Correlation of preoperative serum and peritoneal cytokine values on total patients: IP-10 (a); MIP-1α (b); IL-10 (c)