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OBJECTIVES To study the effect of pentoxifylline and octreotide administration on serum levels of TNF-alpha and IL-6, in patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), whether they developed pancreatitis or not. METHODS Out of 590 patients undergoing ERCP, 30 who developed pancreatitis and 25 who did not (controls) were enrolled. Pentoxifylline was given to 23 patients (15 with and eight without pancreatitis) and octreotide to 19 patients (nine with and 10 without pancreatitis, respectively). Thirteen patients did not receive any preventive medication (six with and seven without pancreatitis, respectively). Blood samples were collected at baseline, 6 and 24 h after ERCP. RESULTS IL-6 increased significantly in patients with pancreatitis at the 6 h (4.2 pg/ml SD: 5.8) and at the 24 h (6.6 pg/ml SD: 9.8) compared with patients without pancreatitis at the 6 h (2.1 pg/ml SD: 3.6) and 24 h (1.9 pg/ml SD: 2.5) (P < 0.01). No significant difference in the values of TNF-alpha and IL-6 obtained among the three study groups in patients with or without pancreatitis was observed. TNF-alpha levels at the 24 h were lower than baseline in patients with pancreatitis who received octreotide (P = 0.04). CONCLUSION IL-6 increased in the first 24 h of post-ERCP pancreatitis. Pentoxifylline and octreotide cannot prevent IL-6 elevation but octreotide reduces TNF-alpha levels, which may have an impact on the severity of post-ERCP pancreatitis.