Nuclear factor kappaB activation in acute appendicitis: a molecular marker for extent of disease?

Nuclear factor-kappaB (NF-kappaB) has been demonstrated to regulate the transcription of target genes and stimulate inflammatory cytokine responses in a variety of inflammatory diseases. Preliminary studies have demonstrated that NF-kappaB is activated early in acute inflammation and sepsis and may serve as an indicator of clinical severity. The present study was designed to evaluate the degree of activation of NF-kappaB in patients with acute appendicitis and correlate activation with clinical extent of disease. Ten patients with acute appendicitis and five control patients (elective inguinal hernia repair) were evaluated by assaying NF-kappaB activity preoperatively and 12 to 18 hours postoperatively. Assaying of NF-kappaB was determined by binding activity for consensus probes in nuclear extracts from peripheral mixed white blood cells obtained by venous puncture. The bands of NF-kappaB activity from gel electrophoresis were quantified with a phosphor imager and reported as units of integrated intensity. The preoperative NF-kappaB activity was increased in all patients with appendicitis versus the controls [mean 151 (range 97-189) vs mean 50.3 (range 13.7-77); P < 0.0001]. The increased NF-kappaB activity also correlated with length of time of symptoms before operation. The patients who were symptomatic for less than 24 hours had an average NF-kappaB value of 103 (range 97-105) versus 171.4 (range 152-189) (P < 0.0001) in those who were symptomatic 24 or more hours. The NF-kappaB activity did not correlate with the white blood cell count. Postoperative NF-kappaB binding activity in the appendicitis patients dropped to minimal levels (mean 50.3), even lower than the control patients' baseline values (mean 55.6). Control patients demonstrated low baseline values preoperatively and a slight rise postoperatively [mean 50.3 (range 13.7-77) vs mean 100 (range 45-186)]. We conclude the following: (1) NF-kappaB binding activity is elevated in patients with acute appendicitis and correlates with symptoms longer than 24 hours. (2) This increased activity returns to baseline values within 18 hours after appendectomy. (3) Molecular indicators of inflammation may have a role in both staging surgical inflammatory conditions and predicting ultimate outcome.