Serum levels of NF-κB and pro-inflammatory cytokines following administration of mucotoxic drugs

Abstract

Introduction:Alimentary tract (AT) mucositis is a serious complication of cancer treatment. Determining changes that occur in the AT can be difficult as invasive procedures are usually contraindicated in these patients. Changes in tissue levels of the transcription factor NF-κB and pro-inflammatory cytokines have been demonstrated. The aims of this study were to determine whether changes in serum levels of NF-κB, TNF, IL-1β and IL-6 following administration of different drugs predicted histological evidence of tissue damage.Materials and Methods:Female DA rats (n=243) were given a single dose of irinotecan (200mg/kg intraperitoneally), methotrexate (1.5mg/kg intramuscularly) or 5-fluorouracil (150mg/kg intraperitoneally) and killed 30, 60, 90 minutes, 2, 6, 12, 24, 48 or 72 hours later. Control rats received no treatment. Blood samples were taken via cardiac puncture and centrifuged at 5000 rpm to collect serum. Serum levels of NF-κB, and pro-inflammatory cytokines were measured by ELISA. Results:Changes in serum levels of NF-κB, TNF, IL-1β and IL-6 were observed following administration of each drug. These changes differed according to the drug administered. In most instances, peaks in serum levels occurred following initial histological changes, Although following MTX administration, serum IL-1β peaked before histological changes and following 5-FU administration, serum NF-κB, TNF, IL-1β and IL-6 all peaked before histological evidence of tissue damage.