Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the senescent remodeling of the immune system with aging and its relevance to the increased susceptibility of the elderly to infectious diseases, along with an outlook on emerging immunological biomarkers.</p><p><b>DATA SOURCES</b>The data selected were from PubMed with relevant published articles in English or French from 1995 to the present. Searches were made using the terms "immunosenescence" and "aging" paired with the following: "innate immunity", "T-cell", "B-cell", "adaptive immunity" and "biomarkers". Articles were reviewed for additional citations and some information was gathered from web searches.</p><p><b>STUDY SELECTION</b>Articles on aging of both the innate and adaptive immunity were reviewed, with special attention to the remodeling effect on the ability of the immune system to fight infectious diseases. Articles related to biomarkers of immunosenescence were selected with the goal of identifying immunological biomarkers predisposing the elderly to infections.</p><p><b>RESULTS</b>Innate immunity is generally thought to be relatively well preserved or enhanced during aging compared with adaptive immunity which manifests more profound alterations. However, evidence, particularly in the last decade, reveals that both limbs of the immune system undergo profound remodeling with aging. Reported data on adaptive immunity is consistent and changes are well established but conflicting results about innate immunity were reported between in vivo and in vitro studies, as well as between murine and human studies. Epidemiological data suggests increased predisposition of the elderly to infections, but no compelling scientific evidence has directly linked senescent immune remodeling to this increased susceptibility. Recently, growing interest in identifying immunological biomarkers and defining "immune risk phenotypes/profiles" (IRP) has been expressed. Identification of biomarkers is in its early days and few potential biomarkers have been identified, with the Swedish having defined one IRP based on the adaptive immune response.</p><p><b>CONCLUSIONS</b>Aging does not necessarily lead to an unavoidable decline in immune functions. Instead, a complex remodeling occurs. Despite the lack of compelling scientific evidence, senescent immune remodeling surely is a significant contributing factor to the increased risk and severity of infections in the elderly. Although, no immunological biomarker has been formally linked to the increased risk of infections in the elderly, biomarkers remain a promising tool to predict the likelihood of healthy aging, the level of immune competence, and mortality risk in the elderly. Hence, more research is required to define healthy aging and identify immunological biomarkers.</p>

Characteristics of lymphocyte nuclear factor-κB signal transduction kinase expression in aging process and regulatory effect of epimedium flavonoids / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the characteristics of lymphocyte nuclear factor kappa B (NF-κB) signal transduction kinase-related molecular mRNA differential expressions at various month age segments in aging process and the intervening effect of Epimedium flavonoids (EF) on it.</p><p><b>METHODS</b>Sixty SD rats were divided into six groups, according to animals' age, i.e., the 3 days (d) group, the 4 months (m) group, the 10 m group, the 18 m group, the 27 m group, and the 27 m+EF group. RNA was extracted from separated splenic lymphocytes. Adopting NF-κB signal path functional genome oligonucleotide gene-chip (128 related genes), the integral characteristics and differences of NF-κB signal transduction kinase-related mRNA expressions were determined, and the intervening effect of EF was examined.</p><p><b>RESULTS</b>The mean level of the NF-κB signal transduction kinase-related mRNA expressions in rats' splenic lymphocytes lowered with aging; the highest expression was presented at 3 d after birth, and then, it lowered gradually, with the lowest level at 18 m or 27 m. After EF intervention, the expression level was raised to the 10-18 m level in the aged rats.</p><p><b>CONCLUSION</b>The changing rules of lymphocyte NF-κB-signal-transduction-kinase-related mRNA expressions in various stages of aging are helpful for selecting the well time for preventing and intervening aging, and will also give a hint to the molecular index for assessment of senility retarding researches.</p>

[Mucosal administration of altered CII263-272 peptide inhibits collagen-induced arthritis].

OBJECTIVE: To evaluate the effect of mucosal administration of altered collagen II(CII)263-272 peptide (267Q-->A, 270K-->A and 271G-->A) on collagen induced arthritis (CIA), and to explore the mechanism of the inhibitory effect of the altered CII263-272 peptide on CIA. METHODS: CIA was induced in Lewis rats by immunization with bovine CII. Altered CII263-272 peptide was given intranasally beginning from the onset of arthritis (100 microg/dose, daily for 5 doses and continuing every other day for other 7 doses). Wild CII263-272 peptide (100 microg/dose) or PBS was administered as controls with the same procedure. Therapeutic effects were evaluated by arthritis scores, body weight change, and joint pathologic scores. The anti-CII antibody and its subtypes were measured with ELISA. The cytokines of IFN-gamma and IL-10 were measured with ELISA. The induction of regulatory T cells was assessed by FACS analysis of percentage of peripheral CD4(+)CD25(+) T cells, and by real-time PCR analysis of the expression of Foxp3 and TGF-beta mRNA. RESULTS: (1) Following treatment with the altered CII263-272 peptide, arthritis scores were reduced and body weight was increased. The mean arthritis scores of rats treated with altered peptide, wild peptide and PBS were 2.50 +/- 2.43, 4.50 +/- 2.23 and 6.33 +/- 2.73, respectively. The altered peptide could retard the histologic lesion of the joints. (2) The titers of anti-CII antibodies IgG and IgG1 in the three groups were similar, but the IgG2a in altered peptide-treated rats decreased markedly as compared with PBS-treated rats (0.56 +/- 0.19 vs 0.95 +/- 0.29, P<0.05). The serum IFN-gamma in rats treated with altered peptide, wild peptide and PBS were (185.33 +/- 29.77), (231.62 +/- 41.82) and (220.64 +/- 83.61) ng/L, respectively (P<0.05). No difference was found in the levels of serum IL-10 among the three groups. (3) There was no significant difference in the percentage of peripheral CD4(+)CD25(+) T cells and the expression level of Foxp3 and TGF-beta mRNA. CONCLUSION: Mucosal administration of altered CII263-272 peptide could effectively inhibit the progression of CIA. It can decrease the IgG2a subtype of anti-CII antibodies and IFN-gamma, and inhibit Th1 response in vivo. Altered C II263-272 peptide may be therapeutic for RA.

Study on changes of protein phosphorylation of p65, IkappaBalpha and IkappaBepsilon in lymphocytes of rats in progress of aging and interventional effect of Epimedium flavonoids / 中国中药杂志

<p><b>OBJECTIVE</b>To study the characteristics of protein phosphorylation of p65, IkappaBalpha and IkappaBepsilon in lymphocytes of rats in the progress of aging and the the interventional effect of Epimedium flavonoids (EF).</p><p><b>METHOD</b>We chose the lymphocytes derived from SD rat spleen. We divided the SD rats into five groups i. e. 4 months (4 m), 27 months (27 m), the 27 m EF treated group (27 m + EF), and we also observed the whole interventional effect of PDTC (a NF-kappaB inhibitor) on old rat groups (27 m PDTC, 27 m PDTC + EF ) when IkappaBepsilon, IkappaBalpha were detected. Through the western-blotting analyses, we studied the entire characteristics and distinctions of phosphorylation expression in molecules related to NF-kappaB signal transduction pathway p65, IkappaBepsilon and IkappaBalpha in lymphocytes across the age spectrum of rats in aging. We also observed the whole interventional effect of EF on lymphocytes of old rats.</p><p><b>RESULT</b>With the increasing of age, the mean level of phosphorylation expressions of p65, IkappaBalpha and IkappaBepsilon in rat spleen lymphocytes decreased obviously, When inhibited NF-kappaB by PDTC, there was decreased evidently, while PDTC + EF can active NF-kappaB family and the above molecules were increased to a certain extent.</p><p><b>CONCLUSION</b>The phosphorylation expressions of p65, IkappaBalpha and IkappaBepsilon in rat spleen lymphocytes were not enouphe, EF have a strong effect to upregulated the expression of them during aging.</p>