IL-8 induces T cell chemotaxis, suppresses IL-4, and up-regulates IL-8 production by CD4+ T cells.
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-gamma, 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 culture of CD4+ T cells, thereby probably inactivating the effect of IL-8 originating from the cultured T cells. Also, we observed that IL-4 mRNA expression was down-regulated 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 microgram/ml) or IL-10 (100 ng/ml) l 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.
Gesser
B
B
Department of Dermatology, Marselisborg Hospital, University of Aarhus, Denmark.
Lund
M
M
Lohse
N
N
Vestergaad
C
C
Matsushima
K
K
Sindet-Pedersen
S
S
Jensen
S L
SL
Thestrup-Pedersen
K
K
Larsen
C G
CG
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D015870:Gene Expression; D006801:Humans; D007111:Immunity, Cellular; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics
D016209:Interleukin-8; D012333:RNA, Messenger; D015847:Interleukin-4