+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist

Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist

Proceedings of the National Academy of Sciences of the United States of America 89(9): 4076-4080

Interleukin 1 receptor antagonist (IL-1ra), a naturally occurring polypeptide with amino acid sequence homology to interleukin 1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta), prevents Escherichia coli-induced shock and death. Both IL-1 and IL-1ra are produced by monocytes stimulated with lipopolysaccharide (LPS). Because interleukin 4 (IL-4) suppresses IL-1 production, we investigated whether IL-4 modulated IL-1ra synthesis in LPS-stimulated human peripheral blood mononuclear cells. IL-1 beta and IL-1ra were measured by specific RIAs. IL-4 alone (0.01-100 ng/ml) did not stimulate IL-1 beta synthesis but rather induced IL-1ra (4.82 +/- 0.94 ng/ml). LPS induced synthesis of both IL-1 beta (6.67 +/- 1.06 ng/ml) and IL-1ra (10.77 +/- 2.79 ng/ml). IL-4 suppressed LPS-induced IL-1 beta mRNA accumulation and synthesis. However, IL-4 acted synergistically with LPS in inducing IL-1ra. IL-4 enhanced LPS-induced IL-1ra mRNA accumulation 4-fold and IL-1ra protein synthesis nearly 2-fold. Moreover, IL-1ra mRNA levels were maximal after 6 hr of exposure to LPS but peaked within the first 3 hr in the presence of IL-4. IL-4 added as late as 12 hr after LPS stimulation still enhanced IL-1ra synthesis. In human peripheral blood mononuclear cells stimulated with IL-1 alpha, IL-4 markedly suppressed IL-1 beta production but enhanced IL-1ra synthesis greater than 2-fold. Because IL-4 favors synthesis of the natural antagonist IL-1ra over synthesis of the agonist IL-1, IL-4 may exert potent antiinflammatory effects on host responses to Gram-negative infections.

(PDF emailed within 0-6 h: $19.90)

Accession: 039687192

Download citation: RISBibTeXText

PMID: 1533284

DOI: 10.1073/pnas.89.9.4076

Related references

Interleukin 1-beta, interleukin 1 receptor antagonist, interleukin 10, and interleukin 13 gene expression in the central nervous system and anterior pituitary during systemic inflammation Pathophysiological implications. Journal of Investigative Medicine 45(3): 238A, 1997

Interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 gene polymorphisms: relationship to occurrence and severity of rheumatoid arthritis. Arthritis and Rheumatism 42(6): 1093-1100, 1999

Interleukin-8 Secretion And 15-Lipoxygenase Acuvtty In Rheumatoid Arthritis: In Vitro Anti-Inflammatory Effects By Interleukin-4 And Interleukin-10, But Not By Interleukin-1 Receptor Antagonist Protein. Rheumatology 33(6): 520-525, 1994

Interleukin-8 secretion and 15-lipoxygenase activity in rheumatoid arthritis: in vitro anti-inflammatory effects by interleukin-4 and interleukin-10, but not by interleukin-1 receptor antagonist protein. British Journal of Rheumatology 33(6): 520-525, 1994

Inhibition of Interleukin-1 (Alpha and Beta), Interleukin-2 Secretion and Surface Expression of Interleukin-2 Receptor (IL-2R) by a Novel Cytokine Interleukin-1 Receptor Antagonist (IL-lra). Scandinavian Journal of Immunology 36(1): 27-34, 1992

Inhibition of interleukin-1 (alpha and beta), interleukin-2 secretion and surface expression of interleukin-2 receptor (IL-2R) by a novel cytokine interleukin-1 receptor antagonist (IL-1ra). Scandinavian Journal of Immunology 36(1): 27-33, 1992

The effects of interleukin-10 on interleukin-1 receptor antagonist and interleukin-1 beta production in human monocytes and neutrophils. Lymphokine and Cytokine Research 13(1): 47-54, 1994

Graves' ophthalmopathy and gene polymorphisms in interleukin-1alpha, interleukin-1beta, interleukin-1 receptor and interleukin-1 receptor antagonist. Clinical and Experimental Ophthalmology 37(6): 614-619, 2009

Spontaneous in vivo gene transcription of interleukin-2, interleukin-3, interleukin-4, interleukin-6, interferon-gamma, interleukin-2 receptor (CD25) and proto-oncogene c-myc by rheumatoid synovial T lymphocytes. Scandinavian Journal of Immunology 36(6): 865-873, 1992

Interleukin-1 down-regulates gene and surface expression of interleukin-1 receptor type I by destabilizing its mRNA whereas interleukin-2 increases its expression. Immunology 75(3): 427-434, 1992

Interleukin 1 induces expression of the human immunodeficiency virus alone and in synergy with interleukin 6 in chronically infected U1 cells: inhibition of inductive effects by the interleukin 1 receptor antagonist. Proceedings of the National Academy of Sciences of the United States of America 91(1): 108-112, 1994

Pre-interleukin-1alpha expression reduces cell growth and increases interleukin-6 production in SaOS-2 osteosarcoma cells: Differential inhibitory effect of interleukin-1 receptor antagonist (icIL-1Ra1). Cytokine 31(2): 153-160, 2005

Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor. Journal of Neuroimmunology 45(1-2): 163-173, 1993

Liposomal muramyl tripeptide up-regulates interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 gene expression in human monocytes. Journal of Pharmacology and Experimental Therapeutics 268(2): 1032-1039, 1994

Interleukin-1β, interleukin-1 receptor antagonist, interleukin-6, interleukin-10, and tumor necrosis factor-α levels in CSF and serum in relation to the clinical diversity of Parkinson's disease. Cellular Immunology 327: 77-82, 2018