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Synergistic effect of IL-4 and TNF-alpha in the induction of monocytic differentiation of a mouse myeloid leukaemic cell line (WEHI-3B JCS).

Synergistic effect of IL-4 and TNF-alpha in the induction of monocytic differentiation of a mouse myeloid leukaemic cell line (WEHI-3B JCS).

Authors :
Leung KN
Mak NK
Fung MC
Hapel AJ
Source :
Immunology [Immunology] 1994 Jan; Vol. 81 (1), pp. 65-72.
Publication Year :
1994

Abstract

We have previously shown that non-cytotoxic concentrations (600-1200 U/ml) of recombinant mouse tumour necrosis factor-alpha (TNF-alpha) can induce differentiation of a subclone (JCS) of the WEHI-3B myelomonocytic leukaemia cell line into mature cells with the characteristics of macrophages. In the present study, the effects of recombinant mouse interleukin-4 (IL-4), either alone or in combination with mouse TNF-alpha, on the growth and differentiation of JCS cells were examined. IL-4 alone (20-5000 U/ml) inhibited the growth of JCS cells in a dose-dependent manner but did not induce cell differentiation. However, combinations of IL-4 and TNF-alpha acted in synergy to inhibit cell proliferation and induce monocytic differentiation of JCS cells, as shown by increased expression of the macrophage differentiation antigens (F4/80, Mac-1), stimulation of phagocytic activity, induction of non-specific esterase and NBT-reducing activities, increased plastic adherence and morphological criteria. Similar synergistic interactions were also shown by human TNF-alpha and mouse IL-4, indicating that TNF-alpha might exert its effects through the low-affinity (p55) TNF receptors. Moreover, the clonogenicity of JCS cells in vitro and their tumorigenicity in vivo were significantly reduced by combined TNF-alpha and IL-4 treatment. Our results indicate that TNF-alpha can act as a differential signal for JCS cells and that its effects are modulated by IL-4. Therefore, the combination of TNF-alpha and IL-4 may be useful in the treatment of some forms of myelomonocytic leukaemia.

Details

Language :
English
ISSN :
0019-2805
Volume :
81
Issue :
1
Database :
MEDLINE
Journal :
Immunology
Publication Type :
Academic Journal
Accession number :
8132222