Spermine differentially regulates the production of interleukin-12 p40 and interleukin-10 and suppresses the release of the t helper 1 cytokine interferon-γ

György Haskó, David G. Kuhel, Anita Marton, Zoltan H. Nemeth, Edwin A. Deitch, Csaba Szabo

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Polyamines are endogenous immunomodulatory molecules. Recent studies revealed that polyamines suppress the production of proinflammatory cytokines and nitric oxide. In the present study, we investigated the effect of the polyamines spermine, spermidine, and putrescine on the production of interleukin (IL)-12 p40, IL-10, and interferon (IFN-γ) in mouse peritoneal macrophages and spleen cell suspensions. Spermine, but not spermidine or putrescine, suppressed, in a concentration-dependent manner, the production of IL-12 p40 by lipopolysaccharide (LPS)-stimulated macrophages. The effect of spermine was post-transcriptional, because steady-state levels of messenger ribonucleic acid (mRNAs) for IL-12 (p35 and p40) were not affected. In contrast to its inhibitory effect on IL-12 p40, spermine (0.3-3 μM) augmented IL-10 production. The down-regulation of IL-12 p40 by spermine was independent of enhancement of IL-10 by this agent, for spermine retained its ability to suppress IL-12 production in peritoneal macrophages obtained from IL-10-deficient mice. The alterations in cytokine production by spermine did not involve an effect on early intracellular pathways of LPS signal transduction, including the p38 or p42/44 mitogen-activated protein kinases, or the c-jun terminal kinase. In spleen cell suspensions, spermine suppressed the release of IFN-γ induced either by LPS or anti-CD3 antibody. In summary, spermine exerts anti-inflammatory effects by suppressing IL-12 and IFN-γ and by augmenting the production of IL-10.

Original languageEnglish (US)
Pages (from-to)144-149
Number of pages6
JournalShock
Volume14
Issue number2
StatePublished - Aug 2000
Externally publishedYes

Fingerprint

Spermine
Interleukin-12
Interleukin-10
Interferons
Cytokines
Polyamines
Lipopolysaccharides
Putrescine
Spermidine
Peritoneal Macrophages
Suspensions
Interleukin-12 Subunit p35
Spleen
adjuvant P40
Mitogen-Activated Protein Kinase 1
Anti-Idiotypic Antibodies
Signal Transduction
Nitric Oxide
Anti-Inflammatory Agents
Phosphotransferases

Keywords

  • Anti-inflammatory
  • Endotoxin
  • Inflammation
  • JNK
  • MAP kinase
  • Pregnancy
  • Proinflammatory
  • T-helper 2
  • Tumor

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Spermine differentially regulates the production of interleukin-12 p40 and interleukin-10 and suppresses the release of the t helper 1 cytokine interferon-γ. / Haskó, György; Kuhel, David G.; Marton, Anita; Nemeth, Zoltan H.; Deitch, Edwin A.; Szabo, Csaba.

In: Shock, Vol. 14, No. 2, 08.2000, p. 144-149.

Research output: Contribution to journalArticle

Haskó, György ; Kuhel, David G. ; Marton, Anita ; Nemeth, Zoltan H. ; Deitch, Edwin A. ; Szabo, Csaba. / Spermine differentially regulates the production of interleukin-12 p40 and interleukin-10 and suppresses the release of the t helper 1 cytokine interferon-γ. In: Shock. 2000 ; Vol. 14, No. 2. pp. 144-149.
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