Regulation of immunomodulatory functions by granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in vivo

The present study was designed to investigate in vivo immunomodulatory properties of hematopoietic growth factors. The influence on the activation of cytokine synthesis and on the expression of surface antigens associated with cellular activation of G-CSF or GM-CSF was investigated in cancer patient...

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Bibliographic Details
Published in:	Annals of hematology Vol. 73; no. 5; pp. 231 - 238
Main Authors:	AMAN, M. J, STOCKDREHER, K, THEWS, A, KIENAST, K, AULITZKY, W. E, FÄRBER, L, HAUS, U, KOCI, B, HUBER, C, PESCHEL, C
Format:	Journal Article
Language:	English
Published:	Berlin Springer 01-11-1996
Subjects:	Adjuvants, Immunologic - pharmacology Adult Aged Antigens, Surface - biosynthesis Biological and medical sciences Granulocyte Colony-Stimulating Factor - pharmacology Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology Growth Substances - genetics Hematopoietic Stem Cells - chemistry Humans Immunomodulators Interleukin 1 Receptor Antagonist Protein Interleukin-6 - blood Interleukin-8 - blood Medical sciences Middle Aged Pharmacology. Drug treatments Receptors, Interleukin-1 - antagonists & inhibitors Receptors, Interleukin-2 - blood Recombinant Proteins - blood RNA, Messenger - metabolism Sialoglycoproteins - blood Solubility Human Lung disease Urinary system disease Carcinoma Respiratory disease Cytokine Biosynthesis Malignant tumor Urinary tract disease Cell surface Bronchopulmonary Antigen Immunomodulator Granulocyte colony stimulating factor Treatment Urinary bladder Bronchus disease Bladder disease Small cell carcinoma Granulocyte macrophage colony stimulating factor
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Summary:	The present study was designed to investigate in vivo immunomodulatory properties of hematopoietic growth factors. The influence on the activation of cytokine synthesis and on the expression of surface antigens associated with cellular activation of G-CSF or GM-CSF was investigated in cancer patients receiving these factors. One single dose of growth factor was administered to patients with bladder cancer (G-CSF group) or small cell lung cancer (GM-CSF group) before chemotherapy. After cytoreductive chemotherapy patients received supportive therapy with G-CSF or GM-CSF. Peripheral blood mononuclear cells and plasma samples were obtained for flow cytometry, Northern blot analysis, and assessment of cytokine protein levels after single-dose as well as after continuous cytokine administration. Our results demonstrate differences in the induction of biological activities by GM-CSF and G-CSF in vivo which correlate well with in vitro findings. Among mature hematopoietic cells the effect of G-CSF is restricted to the granulocyte lineage. With GM-CSF moderate but unequivocal modulation of monocyte function was observed. On peripheral blood monocytes expression of MHC class-II molecules and CD44 was markedly stimulated. After one single dose of GM-CSF, plasma levels of sCD25 and IL-1RA were significantly induced (p < 0.0001, p = 0.032, respectively) and a trend to increased IL-8 levels was observed. The changes in plasma proteins were not correlated with shifts of mRNA expression for IL-8 and IL-1RA. T-cell activation was not observed with either cytokine. These results suggest that immunomodulatory features are differentially regulated by G-CSF and GM-CSF. The clinical relevance of a selective use of both hematopoietic growth factors in various disease settings remains to be determined.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0939-5555 1432-0584
DOI:	10.1007/s002770050234