Interleukin-4 downregulates interleukin-6 production by human alveolar macrophages at protein and mRNA levels.
Effects of interleukin-4 (IL-4) on IL-6 production by human alveolar macrophages (AM) obtained by bronchoalveolar lavage from healthy donors was examined at the protein and gene levels. IL-6 production was quantitated by enzyme immunoassay (EIA) and bioassay using the IL-6 dependent murine hybridoma cell line MH60.BSF2. Results showed that when activated with LPS, AM released significantly more biologically active IL-6 than blood monocytes. Human rIL-4 significantly suppressed IL-6 production by AM and monocytes stimulated with LPS. Northern blot analysis revealed that IL-4 reduced the expression of IL-6 mRNA in LPS-stimulated AM and monocytes. The inhibitory effect was most pronounced when IL-4 was added with LPS or within the first 4 hr after LPS to AM or monocytes. The suppressive effect of IL-4 was completely neutralized by pretreatment with anti-IL-4 antibody. IL-4 also showed a suppressive effect on IL-6 production by macrophages generated in vitro by maturation of blood monocytes with granulocyte-macrophage colony stimulating factor (GM-CSF). These observations suggest that IL-4 may play a critical role in in situ regulation of immune responses through suppression of IL-6 production.
Yanagawa
H
H
Third Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Sone
S
S
Sugihara
K
K
Tanaka
K
K
Ogura
T
T
D000328:Adult; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008262:Macrophage Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis*
D015850:Interleukin-6; D012333:RNA, Messenger; D015847:Interleukin-4