Pentoxifylline in vitro reverses neutrophil chemotactic deficiency induced by interleukin-2 treatment.
Patients undergoing immunotherapy with Interleukin-2 experience multiple side effects and are highly susceptible to bacteremia. In a previous study, we confirmed the profound neutrophil chemotactic deficiency induced by Interleukin-2 therapy. Peripheral blood cells exposed to Interleukin-2 in vitro secrete secondary cytokines. The release of tumor necrosis factor into the circulation after Interleukin-2 injection has been proposed as an important mechanism underlying cell function alterations. We tested chemotaxis of neutrophils from normal subjects after incubation with the serum from treated patients. Serums induced a defective chemotaxis of normal neutrophils similar to the one observed with neutrophils from Interleukin-2 treated patients. We have previously demonstrated a dose-dependent reversion of neutrophil chemotaxis after incubation with anti-Tumor Necrosis Factor-alpha antibody. Pentoxifylline is known for counteracting the inflammatory action of tumor necrosis factor. We tested its capability to reverse the chemotactic deficiency of neutrophils induced by treated patient serums. Pentoxifylline was added after incubation of normal cells with patient serum, and the directed chemotaxis was restored. Pentoxifylline may have a significant therapeutic potential for the prevention or treatment of complications related to inappropriately activated neutrophils.
Fossat
C
C
Laboratoire d'Hématologie, CHU Timone, Marseille, France.
Sainty
D
D
Stoppa
A M
AM
Maraninchi
D
D
Juhan-Vague
I
I
D016470:Bacteremia / Q000209:etiology; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004198:Disease Susceptibility; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000628:therapy; D009369:Neoplasms / Q000628:therapy; D009504:Neutrophils / Q000187:drug effects*; D010431:Pentoxifylline / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007155:Immunologic Factors; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010431:Pentoxifylline