Regulation of cytokine production in aging: Use of recombinant cytokines to upregulate mitogen-stimulated spleen cells

Daniela Frasca, Sabina Pucci, Cristina Goso, Paola Barattini, Simona Barile, Claudio Pioli, Gino Doria

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

We investigated the production of IL-2 and IFN-γ (Th1 type) and IL-4 (Th2 type) cytokines by mitogen-activated spleen cells from young, adult and old mice. Cytokine production was evaluated in culture supernatants by CTLL proliferation (IL-2), ELISA (IFN-γ), CT4.S proliferation (IL-4) and in mRNA extracted from activated CD4 + cells by RT-PCR (IL-2, IFN-γ and IL-4). Results show that the production of IL-2, as protein and mRNA, is profoundly depressed by aging, whereas that of IFN-γ, as protein and mRNA, firstly declines and then increases with age. The production of IL-4, as protein, monotonically declines with aging whereas, as mRNA, firstly decreases and then increases above the level in young mice. Spleen cells in culture were also incubated with mitogens and with a recombinant cytokine (IL-1β, IL-2, IL-3, IL-4, IL-12 or IFN-γ) at various concentrations. It was found that recombinant cytokines by and large enhance cytokine production when the level induced by mitogens only is low. This conclusion applies to IL-2 and IFN-γ production as protein and mRNA. The addition of recombinant cytokines also increases the production of IL-4 at the protein level in spleen cells from old mice but, at the mRNA level, only in spleen cells from young mice. This finding suggests age-related changes in IL-4-specific mRNA transcription rate and post-transcriptional half-life as well as translation kinetics.

Original languageEnglish (US)
Pages (from-to)157-169
Number of pages13
JournalMechanisms of Ageing and Development
Volume93
Issue number1-3
DOIs
StatePublished - Feb 1997
Externally publishedYes

Keywords

  • Aging
  • Cytokines
  • Th1 cells
  • Th2 cells

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience

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