Hematopoietic growth factors are differentially regulated in monocytes and CD4+ T lymphocytes: Influence of IFN-α and interleukin-4

Theresa Tretter, M. Javad Aman, Gesine Bug, Christoph Huber, Christian Peschel

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

We investigated the influence of interferon-α (IFN-α) on the synthesis of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin- 3 (IL-3) by monocytes and activated T helper cells. IFN-α inhibited the production of GM-CSF in unstimulated and lipopolysaccharide (LPS)-activated monocytes to the same extant as was observed in the presence of IL-4. In highly purified CD4+ T cells, which were activated by incubation with immobilized anti-CD3 antibody and anti-CD28, IFN-α reduced production of GM- CSF to 47%. In contrast, GM-CSF production in activated T cells was unaffected by exogenously added IL-4. The production of IL-3 by T helper cells was significantly inhibited by IFN-α as well. IL-3 production by CD3/CD28-stimulated T helper cells was exclusively enhanced by IL-4. The exogenous addition of IL-4 led to a highly significant increase of IL-3 levels in T cell supernatants to 231% of control cultures (range 137%605%), whereas other T cell-derived cytokines, such as IFN-τ, and IL-10, failed to influence IL-3 release. The differential role of IL-4 in IL-3 production was confirmed by the addition of anti-IL-4 antibodies to CD3/CD28-stimulated T cells. Neutralizing anti-IL-4 antibody caused a drastic reduction of IL-3 synthesis by activated T cells, whereas GM-CSF production was independent of neutralization of endogenous IL-4. These experiments define IFN-α as an inhibitory substance for the production of hematopoietic growth factors by activated immune cells. The influence of IL-4 on cytokine synthesis appears to be cell type specific, thus revealing a differential stimulatory effect on IL-3 production.

Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalJournal of Interferon and Cytokine Research
Volume18
Issue number2
DOIs
StatePublished - Feb 1998

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