Granulocyte function is stimulated by a novel hexapeptide, WKYMVm, in chemotherapy-treated cancer patients.

Abstract

Bacterial infections are major life-threatening complications in patients receiving cytotoxic drugs. These infections generally occur during periods of neutropenia. It has been suggested that the incidence of neutropenia correlates with the incidence of infections. A synthetic hexapeptide, WKYMVm, which stimulates phosphoinositide hydrolysis in leukocytes, has been shown to activate microbicidal activities of human polymorphonuclear neutrophils. In this study, we evaluate whether WKYMVm stimulates bactericidal activity in neutrophils obtained from patients who received chemotherapy for solid tumors when they were neutropenic. Eight patients and 11 healthy controls were recruited for the study. Patient neutrophils, on day 0 and at 2 weeks after chemotherapy, were collected. Expression of the WKYMVm peptide receptor, on leukocytes, was analyzed by fluorescein-activated cell sorting. Neutrophil bactericidal assays were performed using both reactive oxygen species generation and intracellular killing. Expression of the WKYMVm peptide receptor on leukocytes showed no difference in the treated patients compared to healthy controls. WKYMVm increased bactericidal activities, in a dose-dependent fashion, of control neutrophils compared to treated patient neutrophils obtained on day 0. WKYMVm markedly stimulated bactericidal activity of treated patient neutrophils obtained at 2 weeks after chemotherapy compared to treated patient neutrophils obtained on day 0. WKYMVm augmented neutrophil bactericidal activity was noted at low concentration but was suppressed at higher concentrations of 5-fluorouracil. WKYMVm augmented neutrophil bactericidal activity was not suppressed by cisplatin. WKYMVm has the potential for increasing neutrophil bactericidal activity in chemotherapy-treated cancer patients.

• Authors: Hawk Kim, Jae Hoo Park, Eun-Hee Lee, Mee-Ja Kim, Sang Kyu Park, Sook-Kyoung Heo, Byung-Sam Kim, Young Joo Min
• Journal: Experimental hematology (Exp Hematol) Vol. 34 Issue 4 Pg. 407-13 (Apr 2006) ISSN: 0301-472X [Print] Netherlands
• PMID: 16569587 (Publication Type: Clinical Trial, Comparative Study, Journal Article)

Chemical References

• Oligopeptides
• Receptors, Cell Surface
• Trp-Lys-Tyr-Met-Val-Met
• Cisplatin
• Fluorouracil

Topics

• Adult
• Aged
• Bacterial Infections (drug therapy, etiology, metabolism, pathology)
• Blood Bactericidal Activity (drug effects)
• Cells, Cultured
• Cisplatin (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Antagonism
• Female
• Fluorouracil (pharmacology, therapeutic use)
• Humans
• Male
• Middle Aged
• Neoplasms (complications, drug therapy, metabolism, pathology)
• Neutropenia (drug therapy, etiology, metabolism, pathology)
• Neutrophil Activation (drug effects)
• Neutrophils (metabolism, pathology)
• Oligopeptides (pharmacology, therapeutic use)
• Receptors, Cell Surface (metabolism)