The immune system in aging: roles of cytokines, T cells and NK cells

Huang, Hai; Patel, Dhavalkumar D.; Mantón, Kenneth G.

doi:10.2741/1521

Cited by 90 publications

(65 citation statements)

References 321 publications

(221 reference statements)

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“…There was a great individual variability in mRNA expression levels of the different cytokines in dogs with FRD, IBD and even in control dogs. Differences in age, growth, sex and (or) nutritional status probably also accounted for the variability in cytokine mRNA profiles, in agreement with studies in humans (Moxley et al, 2002;Grimble, 2003;Huang et al, 2005). However, there were significant gender influences on INF-γ mRNA levels of FRD dogs and on IL-13 mRNA levels in IBD dogs in duodenal samples.…”

Section: Discussionsupporting

confidence: 75%

Cytokine mRNA abundance in intestinal biopsies from dogs with chronic diarrhea

Sauter¹,

Allenspach²,

Blum³

2007

Vet. Med. - Czech

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ABSTRACT:The differentiation between inflammatory bowel disease (IBD) and food responsive diarrhea (FRD) is difficult and no objective markers are available. We postulated that patterns of selected key cytokines would help to objectively differentiate between the two subcategories of chronic enteropathies in dogs. We studied mRNA patterns of selected cytokines in dogs with chronic enteropathies. Ten dogs with FRD (= group FRDbef ) and seven dogs with IBD (= group IBDbef ) were presented for endoscopy at the Small Animal Clinic, University of Bern. A control endoscopy was performed in both groups after treatment with an elimination diet for four weeks (FRDaft) or with an elimination diet combined with prednisolone for 10 weeks (IBDaft). Intestinal control samples of gastrointestinally healthy dogs from an independent study were additionally available. Dogs were clinically examined and scored using the canine IBD activity index (CIBDAI). mRNA abundance of interleukin (IL)-5, -10, -12p40, and -13, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and interferon (IFN)-γ were analyzed in intestinal samples by reverse transcription and real time polymerase chain reaction. Median CIBDAI decreased in FRDaft (P < 0.01) and IBDaft (P = 0.07) during treatment. In duodenum, IL-12p40 mRNA levels tended to be lower in FRDbef than in IBDbef (P = 0.07). The abundance of TNF-α mRNA was higher in IBDbef than in control dogs (P < 0.05). IL-5 mRNA levels decreased in FRD dogs during treatment (P = 0.06), and IL-10 mRNA levels decreased in IBD dogs (P < 0.05). In colon, IL-5 and IL-12p40 mRNA levels were lower in FRDbef than in IBDbef (P < 0.05) and control dogs (P < 0.01). IL-13 mRNA abundance was lower in FRDbef than in control dogs (P < 0.05) and IFN-γ mRNA abundance was lower in FRD and IBD dogs than in control dogs (P < 0.01). Feeding the elimination diet additionally reduced IFN-γ mRNA levels (P < 0.01), but increased TNF-α mRNA levels (P < 0.05) in FRD dogs. In conclusion, mRNA levels of the selected cytokines before treatment did not show clear differences between FRD and IBD dogs.

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Section: Discussionsupporting

confidence: 75%

Cytokine mRNA abundance in intestinal biopsies from dogs with chronic diarrhea

Sauter¹,

Allenspach²,

Blum³

2007

Vet. Med. - Czech

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“…Although the possibility does exist that women in our study with evidence of long-term HPV positivity have repeated viral acquisition over time rather than true viral persistence, our findings suggest that weaker cellular immune function may be strongly associated with length of HPV persistence. Stratification of our data by age indicated that the primary effect was evident among women 65 years of age and older, an age group where immune senescence has been previously reported (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Surprisingly, however, we did not observe evidence of age-related immune decline in our HPV-negative control group.…”

Section: Discussionmentioning

confidence: 95%

“…This second peak in HPV prevalence is poorly understood and could be due to cohort effects, re-exposure through new sexual contacts, and/or physiologic changes at the cervix with aging that increase the efficiency of HPV detectability by current sampling methods (25,26). It has also been suggested that this second peak might occur due to reemergence of latent HPV infections in older women (27), following age-related declines in immunologic competence (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40).…”

Section: Introductionmentioning

confidence: 99%

“…Given that results from our 10,000-women population-based cohort in Guanacaste, Costa Rica indicated a second peak in HPV prevalence among women older than 55 years (41), and that immunologic competence has been reported to decrease with aging (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), we reasoned that targeting women in this age group for our investigation might prove fruitful.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Persistent Human Papillomavirus Infection Is Associated with a Generalized Decrease in Immune Responsiveness in Older Women

et al. 2006

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The development of cervical cancer and its precursors are linked to persistent infection with oncogenic types of human papillomavirus (HPV). Host immune responses seem to be determinants of risk for this disease. However, little is known about the immunologic determinants of HPV persistence. Here, we examined the association between lymphoproliferative responses to antigens/mitogens and persistent HPV infection in women older than 45 years. Women included in this study were participants in a 10,000-woman population-based cohort study of cervical neoplasia in Costa Rica. Women older than 45 years and HPV DNA positive at a screening visit were selected as cases (n = 283). We selected a comparably sized control group of HPV DNA-negative women, matched to cases on age and time since enrollment (n = 261). At an additional clinical visit, women were cytologically and virologically rescreened, and cervical and blood specimens were collected. Proliferative responses to phytohemagglutinin (PHA), influenza virus (Flu), and HPV16 virus-like particle (VLP) were lower among women with persistent HPV infection [median counts per minute (cpm): 72,849 for PHA, 1,241 for Flu, and 727 for VLP] than for the control group (median cpm: 107,049 for PHA, 2,111 for Flu, and 2,068 for VLP). The decreases were most profound in women with long-term persistence and were only observed for the oldest age group (z65 years). Our results indicate that an impairment in host immunologic responses is associated to persistent HPV infection. The fact that effects were evident for all studied stimuli is suggestive of a generalized effect.

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“…These include the balance of the pro-inflammatory/anti-inflammatory pathways, lymphocytes activation and hepatocellular stimulation of acute phase protein synthesis [43]. Studies of the effects of ageing on inflammatory response show interleukin-6 (IL-6) to be an important ''cytokine for gerontologists'' [42,72]. Indeed, an age-related increase of IL-6 concentrations has been found in serum, plasma and supernatants of mononuclear blood cell cultures from elderly people devoid of any overt age-related diseases [44,45], beginning as early as 30-40 years of age [111] and being prominent among men [160] and in centenarians [8].…”

Section: Zinc-interleukin-6 Gene Interactionmentioning

confidence: 99%

Zinc–gene interaction related to inflammatory/immune response in ageing

Mocchegiani

Malavolta

2008

Genes Nutr

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The pivotal role played by zinc-gene interaction in affecting some relevant cytokines (IL-6 and TNF-a) and heat shock proteins (HSP70-2) in ageing, successful ageing (nonagenarians) and the most common age-related diseases, such as atherosclerosis and infections, is now recognized. The polymorphisms of genes codifying proteins related to the inflammation are predictive on one hand in longevity, on the other hand they are associated with atherosclerosis or severe infections. Since the health lifespan has a strong genetic component, which in turn also affected by nutritional factors like zinc, the association of these polymorphisms with innate immune response, zinc ion bioavailability and Metallothioneins (MT) homeostasis is an useful tool to unravel the role played by zinc-gene interactions in longevity, especially due to the inability of MT in zinc release in ageing and chronic inflammation. In ageing, this last fact leads to depressed innate immune response for host defence. In contrast, in very old age the inflammation is lower with subsequent more zinc ion bioavailability, less MT gene expression and satisfactory innate immunity. Therefore, the zinc-gene (IL-6, TNF-a, Hsp70-2) interactions, via MT homeostasis, are crucial to achieve successful ageing. Human genes and longevityAgeing is a universal phenomenon that affects nearly all of animal species. According to Helfand and Rogina [69], ageing can be characterized as: (1) an inevitable consequence of being a multicellular organism; (2) associated with a random, passive decline in function; (3) leading to a global loss of homeostasis over time and (4) mortality increasing with ageing. Evolutionary studies on ageing have drawn the attention on the importance of the genetic mechanisms involved in somatic maintenance and repair that secure longevity [82]. Evidence from model organisms has indicated that subtle variation in the genes can dramatically influence lifespan. However, findings on potential candidate genetic mechanisms determining ageing and lifespan in model organisms are far to explain variations in human populations because phenotypes are critically dependent on the setting in which genes are expressed, while laboratory conditions and modern environments are markedly dissimilar [86]. Genetic analysis of human ageing is mainly approached by searching the genetic basis of susceptibility to major geriatric disorders or the allelic contributions to exceptionally long life span. It is just thanks to these last studies in centenarians populations that several candidate longevity genes or pathways including PON1 [19,130], IGF1/insulin pathway [84,120], elements of lipid metabolism [12], stress response [34] and inflammatory response have been identified [53].Genes related to inflammation and stress response, in particular the pro-inflammatory cytokines IL-1, IL-6, TNFalpha, the anti-inflammatory cytokine IL-10, the HSP70 chaperones and the regulators of trace elements homeostasis, metallothioneins (MT), seem particularly relevant taking into accoun...

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The immune system in aging: roles of cytokines, T cells and NK cells

Cited by 90 publications

References 321 publications

Cytokine mRNA abundance in intestinal biopsies from dogs with chronic diarrhea

Cytokine mRNA abundance in intestinal biopsies from dogs with chronic diarrhea

Persistent Human Papillomavirus Infection Is Associated with a Generalized Decrease in Immune Responsiveness in Older Women

Zinc–gene interaction related to inflammatory/immune response in ageing

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