The effects of interleukin-1 therapy on peripheral blood granulocyte function in humans.
During a phase I trial of interleukin-1 alpha (IL-1 alpha) in patients with ovarian carcinomas, the effects of this treatment on blood granulocyte respiratory burst and locomotive responses were examined. Differences in baseline granulocyte function in patients as well as dose-related effects of IL-1 alpha treatment were observed. Patients enrolled early in the trial (low-dose patients) had significantly lower locomotive responses before treatment than their paired controls; these low responses normalized after 5 days of continuous-infusion IL-1 alpha treatment. Patients enrolled later (high-dose patients) had normal locomotive responses before treatment and IL-1 alpha treatment was associated with suppression of responses to selected stimuli at the end of treatment. Pretreatment respiratory burst responses in both low- and high-dose patient groups were essentially normal, but the rates of granulocyte H2O2 production following phorbol myristate acetate stimulation became significantly less than control values at the end of treatment. In vitro exposure of either patient or control cells to 150 U/ml IL-1 alpha did not alter their locomotive or respiratory burst responses, suggesting the observed in vivo effects were not mediated directly by IL-1 alpha. Treatment with IL-1 alpha is associated with changes in ex vivo granulocyte function that are related to the IL-1 alpha dose. Treatment with low doses of IL-1 alpha may provide a means of normalizing abnormal polymorphonuclear leukocyte function in some patients with ovarian malignancies.
Center for Pediatric Research, Eastern Virginia Medical School, Norfolk 23510.
E S
ES
Buescher
S M
SM
McIlheran
S M
SM
Banks
A P
AP
Kudelka
J J
JJ
Kavanagh
S
S
Vadhan-Raj
D000704:Analysis of Variance; D002465:Cell Movement / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007262:Infusions, Intravenous; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007375:Interleukin-1; D011994:Recombinant Proteins; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042205:methionyl-leucyl-phenylalanine; D006861:Hydrogen Peroxide; D013755:Tetradecanoylphorbol Acetate