TY - JOUR
T1 - Regulation of cytokine production in aging
T2 - Use of recombinant cytokines to upregulate mitogen-stimulated spleen cells
AU - Frasca, Daniela
AU - Pucci, Sabina
AU - Goso, Cristina
AU - Barattini, Paola
AU - Barile, Simona
AU - Pioli, Claudio
AU - Doria, Gino
PY - 1997/2
Y1 - 1997/2
N2 - 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.
AB - 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.
KW - Aging
KW - Cytokines
KW - Th1 cells
KW - Th2 cells
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U2 - 10.1016/S0047-6374(96)01825-8
DO - 10.1016/S0047-6374(96)01825-8
M3 - Article
C2 - 9089580
AN - SCOPUS:0030970254
VL - 93
SP - 157
EP - 169
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
SN - 0047-6374
IS - 1-3
ER -