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Recombinant Human Interleukin‐8 Restores Function in Neutrophils from Patients with Myelodysplastic Syndromes Without Stimulating Myeloid Progenitor Cells
Author(s) -
ZWIERZINA H.,
HOLZINGER I.,
GAGGL S.,
WOLF H.,
SCHÖLLENBERGER S.,
LAM C.,
BAMMER T.,
GEISSLER D.,
LINDLEY I.
Publication year - 1993
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1993.tb02560.x
Subject(s) - progenitor cell , immunology , bone marrow , myelodysplastic syndromes , interleukin 3 , clone (java method) , myeloid , granulocyte macrophage colony stimulating factor , medicine , granulocyte colony stimulating factor , cytokine , biology , stem cell , t cell , immune system , chemotherapy , microbiology and biotechnology , dna , genetics , antigen presenting cell
Prognosis in myelodysplastic syndrome (MDS) is not only correlated closely with blast cell count in bone marrow and chromosomal abnormalities but also correlated with decreased leucocyte count and function leading to acquisition of lethal infections. Recently, clinical trials in MDS have focused on the application of haemopoietic growth factors such as G‐CSF or GM‐CSF, which have proven to increase neutrophil count and function. However, these cytokines carry the risk of stimulating the malignant clone, particularly in patients with increased blast cell count. Therefore, investigation of cytokines which are able to stimulate neutrophil function without the potential risk of stimulating haemopoietic progenitor cells may be relevant for MDS. As the stimulatory effect of interleukin‐8 on neutrophil function is well known, we investigated whether recombinant human IL‐8 is also able to improve the function of neutrophils gained from patients with MDS. Using three different techniques—the E. coli killing assay (8 patients), the production of reactive oxygen as determined by cytochrome c reduction (7 patients) and chemiluminescence (8 patients)—a significant stimulation of neutrophil function at a concentration of 10 nM IL‐8 was found in all test systems. No correlation with FAB classification was evident. On the other hand, IL‐8 only mildly stimulated growth of myeloid progenitor cells in bone marrow culture of healthy individuals and MDS patients. This minimal stimulation was blocked by a neutralizing antibody directed against GM‐CSF, suggesting an indirect effect of IL‐8 via secondary GM‐CSF release. Thus, IL‐8 is able in vitro to repair the functional abnormalities of neutrophils from patients with MDS but has only a marginal influence on myeloid progenitor cells.