Investigations of the lymphokine system in elderly individuals

Sindermann, Jürgen R.; Kruse, Andrea; Frercks, Hans-Joachim; Schütz, Rudolf-M.; Kirchner, Holger

doi:10.1016/0047-6374(93)90066-z

Cited by 94 publications

(39 citation statements)

References 25 publications

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“…This suggests that in young donors, different levels of IL 4 production are determined solely by antigen exposure and amount of memory cells, but that in aged donors, other regulatory mechanisms are operating. Unchanged IL 2 and IFN-gamma production, but significantly decreased IFN-gamma and soluble IL 2 receptor secretion has been reported in German SENIEUR donors (209). Equivalent levels of IL 2 secretion by cells from SENIEUR and JUNIEUR donors has also been reported by others (210).…”

Section: Cytokine Production and Responsementioning

confidence: 61%

“…spontaneous production of IL 8 by monocytes in vitro was reported to be lower in the elderly than in the young, but on stimulation with LPS more IL 8 was produced in elderly males than in young (247). A different study showed that LPS-stimulated monocytes from healthy elderly donors produced smaller amounts of IL 8 (as well as G-CSF, GM-CSF, IL 1ß, TNF-ß and MIP-1alpha) than young donors (121), while other studies suggested increased production of IL 6, IL 8 and TNF-alpha by the elderly (209,248) and unchanged IL 12 (122). On the other hand, the dose of LPS required to stimulate IL 6 and TNF production may be greater for monocytes of elderly compared to young donors (249).…”

Section: Cytokine Production and Responsementioning

confidence: 91%

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T cells and aging (update February 1999)

Pawelec

1999

Front Biosci

113

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T cell immunosenescence 218effects of dysregulated immune responses in the elderly by supplementation or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age. FACTORS CONTRIBUTING TO IMMUNO-SENESCENCE HematopoiesisDysregulated hematopoiesis is seen in elderly individuals, raising the possibility that this could contribute to altered immune function in the aged. Hematopoiesis in man may be compromised because of a severely reduced capacity to produce colony stimulating factors (44) and increased production of pro-inflammatory factors such as IL 6 (45), because lower numbers of progenitor cells are present in the BM (46) and because of an age-related decline in proliferative potential of putative haematopoietic stem cells (HSC) (47). In mice, the repopulating potential of murine fetal liver-derived HSC is higher than that of adult BM-derived stem cells (48), suggesting possible aging of the HSC themselves. Normal cells with shorter telomeres possess less remaining replicative capacity than those with longer telomeres (see section 5.2). Accordingly, HSC from adult BM were found to have shorter telomeres than fetal liver-derived or umbilical cord-derived stem cells, consistent with aging of HSC (49). Telomere lengths decreased on culture despite low level expression of telomerase in these cells (50,51), although the rate of basepair loss per population doubling of cells in culture was lower during the first two weeks, when telomerase was upregulated, than in the next two, when it was downregulated (52). The telomerase expressed is therefore functionally active but may not be able to completely maintain telomere length in aging HSC cells. True embryonic stem cells (ESC), on the other hand, which may really be immortal, do retain high levels of telomerase activity (53). On the other hand, ESC from telomerase-knockout mice show gradual telomere shortening over many population doublings (PD) resulting in slowing and eventual cessation of growth (54). Certain animals which do not downregulate telomerase manifest a permanent growth phase and little or no senescence (55,56).

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Section: Cytokine Production and Responsementioning

confidence: 61%

Section: Cytokine Production and Responsementioning

confidence: 91%

T cells and aging (update February 1999)

Pawelec

1999

Front Biosci

113

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“…Previous studies have shown that lymphocytes from the elderly produced significantly less IL-2 and IFN-γ, known as the most important T cell growth factors, than the lymphocytes from young adults (Gillis et al, 1981;Born et al, 1995;Huang et al, 1992;Sindermann et al, 1993;Kita et al, 1991;Paganelli et al, 1996). As shown in Fig.…”

Section: Restorative Effect Of Hemohim On the Responses Of Lymphocytementioning

confidence: 69%

Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM

Park¹,

Jo²,

Jung³

et al. 2007

Phytotherapy Research

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The effect of a new herbal composition, HemoHIM, on immune functions was examined in aged mice, in which various immune responses had been impaired. The composition HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Supplementation to the aged mice with HemoHIM restored the proliferative response and cytokine production of splenocytes with a response to ConA. Also, HemoHIM recovered the NK cell activity which had been impaired in the aged mice. Meanwhile aging is known to reduce the Th1-like function, but not the Th2-like function, resulting in a Th1/Th2 imbalance. HemoHIM restored the Th1/Th2 balance in the aged mice through enhanced IFN-γ γ γ γ γ and IgG2a production, and conversely a reduced IL-4 and IgG1 production. It was found that one factor for the Th1/Th2 imbalance in the aged mice was a lower production of IL-12p70. However, HemoHIM restored the IL-12p70 production in the aged mice. These results suggested that HemoHIM was effective for the restoration of impaired immune functions of the aged mice and therefore could be a good recommendation for immune restoration in elderly humans.

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“…Aging is associated with decreased T-cell activity and proliferative responses to mitogens (28,42) as well as with complex changes in the cytokine network (10,18,37). The production and utilization of some cytokines decrease with age, whereas the production of other cytokines increases.…”

Section: Fig 3 Linear Regression Analysis Showing the Relationship mentioning

confidence: 99%

“…Indeed, there is a shift in number and activity of B lymphocytes, from B2 to B1 lymphocytes (19), that produce polyreactive autoantibodies encoded by variable region genes in a germ line configuration (11). Aging is also associated with complex changes in the cytokine network (10,18,30,37). To understand the mechanisms responsible for these complex changes and to evaluate strategies that can be used to manipulate the immune response in elderly individuals, it is necessary to develop animal models of human aging.…”

mentioning

confidence: 99%

Lymphocyte Modulation in a Baboon Model of Immunosenescence

Jayashankar¹,

Brasky

Ward

et al. 2003

Clin Vaccine Immunol

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The age-related modulation of lymphocyte number and function was assessed in a nonhuman primate model consisting of healthy olive baboons (Papio cynocephalus anubis) of ages encompassing the entire life span of this species. The objectives of this study were to characterize an animal model of immunosenescence and to assess whether or not age should be considered when designing studies for the evaluation of vaccine candidates in baboons. Specifically the following parameters were assessed in baboons from 6 months to 26 years of age: relative numbers of B lymphocytes, CD4؉ and CD8 ؉ T lymphocytes, and T lymphocytes expressing CD28, CD25, and phytohemagglutinin-stimulated lymphoproliferative activity; and concentrations of total immunoglobulin, soluble interleukin-2 receptor ␣, and soluble CD30 in serum. There was a statistically significant effect of age on lymphocyte numbers. As age increased, relative B-cell numbers (ranging from 6 to 50%) decreased (P < 0.001) and relative T-cell numbers (ranging from 28 to 80%) increased (P < 0.001). The increase in T-cell numbers involved both the CD4 ؉ and CD8 ؉ subsets. In addition, there was a significant negative correlation of age with levels of soluble interleukin-2 receptor ␣ in serum. Modulation of lymphocyte numbers appears to occur gradually during the entire baboon life span, thus suggesting the presence of an age-related developmentally regulated process. These findings indicate that baboons represent a potentially useful model to study selected phenomena related to immunosenescence. These findings also indicate that, when using the baboon model for vaccine or other experimental protocols requiring the assessment of immune responses, it would be appropriate to take into account the age of the animals in the study design.The immune system undergoes several functional changes during the aging process. These changes are thought to lead to an age-related increase in susceptibility to infectious diseases, autoimmune disorders, and cancer (26). Both humoral and cellular immune responses are subjected to age-related alterations, including decreased T-and B-cell responses to foreign antigens and increased responses to self-antigens (1,26,28,40). Decreased responses to foreign antigens are associated with the increased morbidity and mortality from infectious diseases as well as with the low vaccine efficacy observed in individuals over 65 years of age (41). The most striking evidence of the changing T-cell compartment is provided by thymic involution, which leads to decreased production of naive T lymphocytes and therefore to limited diversity of the T-cell receptor, although thymic output is present at high levels in elderly individuals (1). The dysregulated humoral immunity is characterized by decreased production of antibodies to most foreign antigens and increased production of autoantibodies. Indeed, there is a shift in number and activity of B lymphocytes, from B2 to B1 lymphocytes (19), that produce polyreactive autoantibodies encoded by variable region genes in a g...

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Investigations of the lymphokine system in elderly individuals

Cited by 94 publications

References 25 publications

T cells and aging (update February 1999)

T cells and aging (update February 1999)

Restoration of the immune functions in aged mice by supplementation with a new herbal composition, HemoHIM

Lymphocyte Modulation in a Baboon Model of Immunosenescence

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