Pentoxifyllin attenuates the systemic inflammatory response induced during isolated limb perfusion with recombinant human tumor necrosis factor-alpha and melphalan.
BACKGROUND
Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor-alpha (rhTNF-alpha) and melphalan harbors the risk of septic shock-like syndrome. Pentoxifyllin (PTX) produced a beneficial effect on cytokine response and survival in animal experiments of septic shock, and we were interested to explore its effect during TNF-ILP in humans.


METHODS
Eighteen consecutive patients underwent TNF-ILP and received PTX (30 mg/kg/day), whereas another 13 consecutive patients did not. PTX was given systemically after the limb extracorporeal circulation was started. Cardiac index, systemic vascular resistance (SVR), and pulmonary vascular resistance were recorded via a Swan-Ganz catheter. Blood levels of TNF-alpha, interleukin-6, procalcitonin, and lipopolysaccharide-binding protein were determined before, during, and after ILP.


RESULTS
After reperfusion, systemic levels of TNF-alpha were significantly less increased in the PTX group (peak, 2.8 vs. 1.3 ng/mL; P <.05), as were interleukin-6 values (peak, 68 vs. 22 pg/mL; P <.02) and lipopolysaccharide-binding protein plasma levels (peak, 215 vs. 105 micro g/mL; P <.03). Differences in cardiac index, SVR, and mean arterial blood pressure were not significantly different. Norepinephrine or dobutamine to maintain SVR was less required in the PTX group.


CONCLUSIONS
PTX attenuates systemic cytokine production and influences components of the systemic inflammatory response after TNF-ILP. PTX may play a beneficial role in the management of septic shock-like syndrome, particularly in patients with leakage from the ILP circuit.
Hohenberger
Peter
P
Division of Surgery and Surgical Oncology, Robert Rössle Hospital and Tumor Institute, Max Delbrück Center for Molecular Medicine, Berlin, Germany. hohenberger@rrk-berlin.de
Latz
Eicke
E
Kettelhack
Christoph
C
Rezaei
Amir-Hossein
AH
Schumann
Ralf
R
Schlag
Peter M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D010478:Chemotherapy, Cancer, Regional Perfusion; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005121:Extremities / Q000098:blood supply; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D008875:Middle Aged; D010431:Pentoxifylline / Q000494:pharmacology*; D012509:Sarcoma / Q000188:drug therapy*; D012772:Shock, Septic / Q000139:chemically induced* / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D008558:Melphalan; D010431:Pentoxifylline