title: Interleukin 13 inhibits macrophage inflammatory protein-1 alpha production from human alveolar macrophages and monocytes.
abstract: Interleukin 13 (IL-13) is a recently described protein secreted by activated T cells and is a potent in vitro modulator of human monocyte and B-cell functions. IL-13 shares some biologic properties as well as structural similarities with IL-4. Macrophage-inflammatory protein 1 alpha (MIP-1 alpha) is a product of activated monocytes and macrophages and an important activator of T cells, monocytes, and macrophages. We determined the effect of human recombinant IL-13 on lipopolysaccharide (LPS)- and IL-1 beta-induced MIP-1 alpha mRNA and protein expression from peripheral blood monocytes (PBM) and alveolar macrophages (AM). In PBM, basal MIP-1 alpha protein was 20 +/- 7 pM and increased following LPS and IL-1 beta to 1,520 +/- 193 (P < 0.001) and 233 +/- 50 (P < 0.003) pM. IL-13 (25 ng/ml) reduced these values by 55 +/- 10% [not significant (NS)], 43 +/- 9% (P < 0.03), and 44 +/- 15% (NS), respectively. LPS- and IL-1 beta-induced MIP-1 alpha mRNA expression was reduced by 43 +/- 5% (P < 0.01) and 41 +/- 4% (NS). In AM, IL-13 reduced LPS-induced MIP-1 alpha protein release of 2,030 +/- 242 pM by 32 +/- 8% (P < 0.05) and MIP-1 alpha mRNA by 27 +/- 1% (NS). For both PBM and AM, the inhibitory effect of IL-13 on MIP-1 alpha protein was maximal at 24 h, was dose dependent with a maximal effect at 100 ng/ml, and was similar to, although slightly less potent than, that seen with IL-4. In PBM, the inhibitory effect of IL-13 required de novo protein synthesis and was not due to enhanced mRNA decay. Thus, IL-13 has inhibitory effects on the transcription of MIP-1 alpha from monocytes and macrophages, and as is the case with IL-4 and IL-10, may be an important mediator for suppressing inflammatory responses.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute, Royal Brompton Hospital, London, United Kingdom.
authors.forename: N
authors.initials: N
authors.lastname: Berkman
authors.forename: M
authors.initials: M
authors.lastname: John
authors.forename: G
authors.initials: G
authors.lastname: Roesems
authors.forename: P
authors.initials: P
authors.lastname: Jose
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
mesh_terms: D015152:Blotting, Northern; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000096:biosynthesis*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006131:Growth Inhibitors; D018793:Interleukin-13; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D003513:Cycloheximide