In vitro inhibition of interleukin-2-induced defective polymorphonuclear chemotaxis by TNF inhibitor.
Patients undergoing immunotherapy with interleukin-2 experience multiple side effects and are highly susceptible to bacteremia. In a previous study, we confirmed that a profound deficiency of neutrophil chemotaxis is induced by interleukin-2 therapy. Migration in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), being normal before therapy, was markedly impaired after the first cycle and further decreased after the third cycle of treatment. A direct effect of interleukin-2 on neutrophil chemotaxis is controversial. However, peripheral blood cells exposed to interleukin-2 secrete secondary cytokines. In particular, the release of tumor necrosis factor after interleukin-2 injection has been proposed as an important regulatory mechanisms. When testing random migration and chemotaxis of neutrophils from normal subjects after incubation with the serum from treated patients, we found that this serum induced a defective chemotaxis similar to that of neutrophils from interleukin-2-treated patients. In order to assess the influence of tumor necrosis factor, we tested the effect of anti-tumor necrosis factor-alpha antibody on the chemotactic response of cells after incubation with the serum, and we observed a dose-dependent reduction of neutrophil chemotaxis deficiency. These data suggest that TNF is counteracting the neutrophil chemotactic deficiency observed during IL-2 treatment.
Fossat
C
C
Laboratory of Haematology, CHU Timone, France.
Sainty
D
D
Stoppa
A M
AM
Blaise
D
D
David
M
M
Maraninchi
D
D
Juhan-Vague
I
I
D000328:Adult; D000906:Antibodies / Q000494:pharmacology*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000097:blood / Q000628:therapy; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000628:therapy*; D008297:Male; D008545:Melanoma / Q000097:blood / Q000628:therapy; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009369:Neoplasms / Q000097:blood / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012509:Sarcoma / Q000097:blood / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine