Effect of age on chronic inflammation and responsiveness to bacterial and viral challenges

Abstract

To identify reliable biomarkers of age-related changes in chronic inflammation and responsiveness to bacterial and viral challenges, we evaluated endogenous and ex vivo stimulated levels of 18 inflammatory markers, using whole blood collected in EDTA and sodium heparin tubes from 41 healthy volunteers, i.e., 11 men + 10 women aged 20–35 and 10 men + 10 women aged 50–77. These studies revealed significant differences in the levels of inflammatory markers when blood was collected in EDTA versus sodium heparin and age related differences in these biomarkers were confirmed with blood collected in EDTA from 120 healthy volunteers in 3 age categories, ie, 20 men + 20 women, aged 20–35, 36–49 and 50–77. Studies with unstimulated blood samples, to measure levels of chronic inflammation, revealed a significant increase with age in IL-12p70, CRP and PGE2, consistent with the concept of “inflammaging”, and a decrease in G-CSF in both men and women. Interestingly, in response to E. coli stimulation, PGE2 levels were markedly reduced in the 50–77 year old cohort while they were increased following Herpes Simplex virus-1 (HSV-1) stimulation, along with IL-8. In addition, unlike E. coli, HSV-1 potently stimulated IFNα production, but levels were dramatically reduced in the older cohort, consistent with a reduced ability to generate an anti-viral response. We also found platelets and CD8+ T cells were reduced with age while CD4+ T cells were significantly increased, resulting in a substantially higher CD4/CD8 ratio in the older cohort. Surprisingly, however, we found that the older cohort exhibited more T cell proliferation and IFNγ production in response to anti-CD3+anti-CD28 stimulation. Importantly, there was considerable person-to-person variation in these inflammatory markers in all age groups, making possible comparisons between a person’s “inflammage” and chronological age. These assays should help to identify individuals at high risk of autoimmune disorders and cancer.

T lymphocyte phenotype of contact‐allergic patients: experience with nickel and p‐phenylenediamine

“…This is consistent with previous studies of healthy donors, in which ratios of 2.0 and 2.3 were observed. 25,26 In the nickel-allergic cohort, a significant decrease in the CD4 + /CD8 hi ratio was shown in strongly allergic individuals (++; P < 0.05), whereas, in the PPD-allergic donors, there was a marked decrease in the CD4 + /CD8 hi ratio in the weakly, strongly and extremely allergic cohorts (combined population as compared with buffy coat samples; P < 0.001). To complement the previous studies of T cell dynamics in allergy to MI, the ratio of CD4 + to CD8 hi cells was measured for an additional cohort of 27 MI-allergic individuals (+, 14; ++, 7; +++, 6).…”

Exploratory examination of inflammation state, immune response and blood cell composition in a human obese cohort to identify potential markers predicting cancer risk

“…ELISAs for prostaglandin E 2 (PGE 2 ) (Cat #514010, Cayman Chemical Company, Ann Arbor, MI), using EDTA-containing blood and C-reactive protein (CRP) (Cat # DCRP00, R&D Systems, Minneapolis, MN), using heparin-containing blood [7] were performed according to the manufacturers' instructions.…”

“…With this in mind, we recently optimized assays to measure an individual's level of CI and immune function and investigated how these change with age in healthy volunteers with normal body mass indexes (BMIs) (within the 18.5-24.9 range) [7]. In the current study, we used these assays to compare participants with BMIs>35 to normal BMI controls.…”

“…However, an overly robust response might indicate an increased susceptibility to autoimmune diseases and cancer. As well, since some studies have suggested that obesity leads to an immunosenescent profile similar to that seen in normal aging [9,10] we set out in the current study to (a) compare levels of CI, immune function and blood cell components in participants with BMIs>35 to people with normal BMIs and to (b) compare results obtained from this cohort to previously published data from our normal aging study [7]. The ultimate aim of these studies is to identify novel markers that are characteristic of people with a BMI>35 and determine if they can be used, in the future, to predict cancer risk.…”

Immune System Sex Differences May Bridge the Gap Between Sex and Gender in Fibromyalgia

“…Sixthly, the immune response is age dependent (Elisia et al, 2017) and age has is a risk factor for loss of central tolerance. In over 60% of autoimmune cases, the onset of symptoms was in the fourth and fifth decade of life, with a median onset at 37.5 years of age (Euesden et al, 2017).…”