Interleukin (IL) 4 differentially regulates monocyte IL-1 family gene expression and synthesis in vitro and in vivo

doi:10.1084/jem.177.3.775

This Article

	Full Text (PDF, 1002K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Wong, H. L.
	Articles by Wahl, S. M.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Wong, H. L.
	Articles by Wahl, S. M.


Social Bookmarking

	What's this?

ARTICLES

Interleukin (IL) 4 differentially regulates monocyte IL-1 family gene expression and synthesis in vitro and in vivo

HL Wong, GL Costa, MT Lotze and SM Wahl
Laboratory of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.

Interleukin (IL) 4 is a multifunctional T cell-derived cytokine that inhibits cytokine production and certain effector functions in human monocytes, while enhancing others. We show that IL-4 may contribute to the downregulation and resolution of an inflammatory response by selectively promoting expression of the IL-1 receptor antagonist (IL- 1ra) that blocks the action of IL-1. IL-1ra specifically binds to the IL-1 receptor without initiating signal transduction. Peripheral blood monocytes obtained from cancer patients, before and immediately after a regimen of IL-4 immunotherapy, were examined for IL-1ra gene expression. After IL-4 therapy, monocytes from the patients showed a marked increase in IL-1ra mRNA. This selective induction of IL-1ra mRNA in circulating monocytes was reflected by significantly enhanced serum levels of IL-1ra (p < 0.01) during IL-4 therapy, which declined after IL-4 treatment. In vitro analysis of IL-4 regulation of monocytes from normal individuals revealed a dose-dependent induction of IL-1ra mRNA within 2-4 h after stimulation without a concomitant effect on the expression of IL-1 mRNA. Increased IL-1ra mRNA was not due to RNA stabilization, but occurred at the level of transcription. In the presence of LPS, IL-4 not only augmented IL-1ra levels, but markedly inhibited LPS-induced IL-1 mRNA expression. The selective upregulation of IL-1ra by resting or activated monocytes, coupled with inhibition of IL-1 production by activated monocytes, as we demonstrate both in vitro and in vivo, suggests that IL-4 may prove clinically useful as a systemic antiinflammatory agent.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Skapenko, A., Niedobitek, G. U., Kalden, J. R., Lipsky, P. E., Schulze-Koops, H. (2004). Generation and Regulation of Human Th1-Biased Immune Responses In Vivo: A Critical Role for IL-4 and IL-10. J. Immunol. 172: 6427-6434 [Abstract] [Full Text]
Huaux, F., Liu, T., McGarry, B., Ullenbruch, M., Phan, S. H. (2003). Dual Roles of IL-4 in Lung Injury and Fibrosis. J. Immunol. 170: 2083-2092 [Abstract] [Full Text]
Sasaki, H., Hou, L., Belani, A., Wang, C.-Y., Uchiyama, T., Muller, R., Stashenko, P. (2000). IL-10, But Not IL-4, Suppresses Infection-Stimulated Bone Resorption In Vivo. J. Immunol. 165: 3626-3630 [Abstract] [Full Text]
McGuirk, P., Mills, K. H. G. (2000). A Regulatory Role for Interleukin 4 in Differential Inflammatory Responses in the Lung following Infection of Mice Primed with Th1- or Th2-Inducing Pertussis Vaccines. Infect. Immun. 68: 1383-1390 [Abstract] [Full Text]
Ohmori, Y., Hamilton, T. A. (1998). STAT6 Is Required for the Anti-inflammatory Activity of Interleukin-4 in Mouse Peritoneal Macrophages. J. Biol. Chem. 273: 29202-29209 [Abstract] [Full Text]
Sauer, J., Renner, U., Hopfner, U., Lange, M., Müller, A., Strasburger, C. J., Pagotto, U., Arzt, E., Stalla, G. K. (1998). Interleukin-1{beta} Enhances Interleukin-1 Receptor Antagonist Content in Human Somatotroph Adenoma Cell Cultures. J. Clin. Endocrinol. Metab. 83: 2429-2434 [Abstract] [Full Text]
Saleem, S., Dai, Z., Coelho, S. N., Konieczny, B. T., Assmann, K. J. M., Baddoura, F. K., Lakkis, F. G. (1998). IL-4 Is an Endogenous Inhibitor of Neutrophil Influx and Subsequent Pathology in Acute Antibody-Mediated Inflammation. J. Immunol. 160: 979-984 [Abstract] [Full Text]