IL-8 induces T cell chemotaxis, suppresses IL-4, and up-regulates IL-8 production by CD4+ T cells

B. Gesser, Marianne Lund, N. Lohse, C. Vestergaard, K. Matsushima, S. Sindet Pedersen, S.L. Jensen, K. Thestrup Pedersen, C.G. Larsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Interleukin-8 (IL-8), a neutrophil-activating cytokine, also activates certain T cell functions such as chemotaxis. We additionally find (n = 6) that recombinant (rIL-8, 1-100 ng/ml), when added to 24 h culture of human CD4+ T cells, suppressed the spontaneous production of IL-4 (50-85%). Steady state production of IL-4 was typically around 30 pg/ml, determined by use of a solid-phase immunoabsorbant assay. De novo synthesis of IL-4 from CD4+ T cells cultured for 3 days was also evaluated by use of detection of [35S]methionine incorporation, as visualized by autoradiography of 2-D gels, and showed that IL-8 suppressed IL-4 production. This suppression of IL-4 production was confirmed in the cytosol fraction by use of Western blotting. The effect of IL-8 (100 ng/ml) was comparable to that of 10 ng/ml recombinant interferon-γ, both strongly suppressing IL-4 production. The regulatory effect of IL-8 on IL-4 production was also indicated by the fact that addition of a neutralizing monoclonal anti-IL-8 antibody (WS.4) enhanced the spontaneous IL-4 production when added to the cultures of CD4+ T cells, thereby probably inactivating the effect of IL-8 originating from the cutured T cells. Also, we observed that IL-4 mRNA expression was downregulated when the CD4+ T cells were cultured for 12 h in the presence of 100 ng/ml IL-8. The suppression of IL-4 mRNA expression could be prevented by adding anti-IL-8 (20 μg/ml) or IL-10 (100 ng/ml) 1 h before adding rIL-8. Thus, IL-8 may be an important regulator of CD4+ T cell-derived IL-4, thereby possibly regulating the balance between humoral and cellular T cell-dependent responses.
Original languageEnglish
JournalJournal of Leukocyte Biology
Volume59
Issue number3
Pages (from-to)407-411
ISSN0741-5400
DOIs
Publication statusPublished - 1996
Externally publishedYes

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