Nuclear factor kappa B activation in acute appendicitis: A molecular marker for extent of disease?

Nuclear factor kappa B (NF-kappa B) has been demonstrated to regulate the t ranscription of target genes and stimulate inflammatory cytokine responses in a variety of inflammatory diseases. Preliminary studies have demonstrate d that NF-kappa B is activated early in acute inflammation and sepsis and m ay serve as an indicator of clinical severity. The present study was design ed to evaluate the degree of activation of NF-kappa B in patients with acut e appendicitis and correlate activation with clinical extent of disease. Te n patients with acute appendicitis and five control patients (elective ingu inal hernia repair) were evaluated by assaying NF-kappa B activity preopera tively and 12 to 18 hours postoperatively. Assaying of NF-kappa B was deter mined by binding activity for consensus probes in nuclear extracts from per ipheral mixed white blood cells obtained by venous puncture. The bands of N F-kappa B activity from gel electrophoresis were quantified with a phosphor imager and reported as units of integrated intensity. The preoperative NF- kappa B 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-kappa B 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-kappa B value of 103 (range 97-105) versus 171. 4 (range 152-189) (P < 0.0001) in those who were symptomatic 24 or more hou rs. The NF-kappa B activity did not correlate with the white blood cell cou nt. Postoperative NF-kappa B 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 v alues 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-kappa B binding activity is elevated in patients with acute appendicitis and cor relates with symptoms longer than 24 hours. (2) This increased activity ret urns to baseline values within 18 hours after appendectomy. (3) Molecular i ndicators of inflammation may have a role in both staging surgical inflamma tory conditions and predicting ultimate outcome.