Age differences in cytokine expression under conditions of health using experimental pain models

Cruz-Almeida, Yenisel; Aguirre, Maria; Sorenson, Heather L.; Tighe, Patrick J.; Wallet, Shannon M.; Riley, Joseph L.

doi:10.1016/j.exger.2015.09.017

Cited by 29 publications

(30 citation statements)

References 49 publications

(48 reference statements)

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“…Detailed health and demographic data for these participants have been previously reported 4. Half of the participants were nonpregnant females of Caucasian origin, and the younger individuals were undergraduate students at the University of Florida.…”

Section: Resultsmentioning

confidence: 99%

“…Along those lines, we have previously reported age-related differences in blood cytokines after experimental pain,4 but it is not currently known whether these differences can be equally measured in saliva samples. The use of saliva as a reliable substitute for blood would provide an avenue for biomarker measurement in large community-based pain studies that would otherwise not be feasible (i.e., putting a central line in community-dwelling older adults for repeated biomarker measurements).…”

Section: Introductionmentioning

confidence: 99%

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Age differences in salivary markers of inflammation in response to experimental pain: does venipuncture matter?

Cruz-Almeida

Aguirre

Sorenson³

et al. 2017

JPR

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An important consideration in mechanistic research using biomarkers should include the use of saliva as an alternative to blood. The use of saliva would allow the study of susceptible populations such as older adults where venipuncture may not be feasible. Although saliva has been most commonly used to measure cortisol and tumor necrosis factor-α (TNFα), there is limited evidence that other cytokines found in saliva significantly change in response to laboratory-induced pain. Therefore, the aim of the current preliminary study was to characterize the time course, duration and magnitude of changes of commonly measured pro- (interleukin [IL]-6, IL-8) and anti-inflammatory (IL-10, IL-4) cytokines in saliva samples and to test for age-related differences in separate experimental painful and non-painful control sessions. In addition, we also tested whether venipuncture results in significant cytokine alterations similar to a painful stimulus in a non-painful, non-venipuncture control session. All cytokines were significantly induced by the cold pressor task compared to a warm control session (p < 0.001). Specifically, healthy older adults experienced greater salivary changes in all cytokines during the cold pressor session compared to younger adults in the non-painful sessions (p < 0.001). There were no significant differences between the venipuncture and non-venipuncture sessions across all cytokines (p > 0.05). Our findings support the use of saliva as a substitute for blood in both young and older healthy individuals to measure changes after experimental pain stimulation. In addition, venipuncture alone is not sufficient to induce IL-6, IL-8, IL-10 and IL-4. Future studies in the community are urgently needed to validate and further move translational mechanistic pain research to those populations most underrepresented in clinical research.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Age differences in salivary markers of inflammation in response to experimental pain: does venipuncture matter?

Cruz-Almeida

Aguirre

Sorenson³

et al. 2017

JPR

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“…We examined patients in the early state of IS who had received drugs that could have influenced the results. Age and major cardio-and cerebrovascular risk factors such as diabetes and smoking an also alter the concentrations of cytokines (10)(11)(12)(13). However, the aim of the present study was to focus on any differences in GCF and serum cytokine concentrations between IS patients and controls.…”

Section: Discussionmentioning

confidence: 96%

IL-1β, TNF-α, and IL-6 levels in gingival fluid and serum of patients with ischemic stroke

2016

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It has been documented that an increaseof immune cells in periodontitis may stimulate the process of atherosclerosis and lead to ischemic stroke. The aim of this study was to investigate whether there is any significant difference in serum and gingival crevicular fluid (GCF) cytokine concentrations between patients with early ischemic stroke (IS) and a control group. Eighty-six patients were consecutively enrolled for this study, 50 with ischemic stroke and 36 as a control group with no previous stroke. Only dentulous patients were included. In each patient, GCF was collected from the deepest periodontal pocket. Blood serum samples were also taken from all subjects. The collected material was analyzed for cytokine concentrations using the cytometric bead array technique. Cerebral ischemia was found to be correlated with higher serum levels of IL-1β (13.01 ± 13.87 vs. 7.83 ± 2.11) and IL-6 (15.82 ± 16.64 vs. 6.64 ± 2.5) compared to the control group. The levels of IL-1, IL-6 and TNF-α in GCF were higher in patients with ischemic stroke but the difference was not significant. In conclusion, ischemic stroke was found to be associated with higher levels of IL-1β and IL-6 in serum. The cytokine concentrations in GCF did not appear to be directly correlated with those in serum in patients with ischemic stroke. (J Oral Sci 58, 509-513, 2016) Keywords: stroke; periodontal disease; cytokines. IntroductionPeriodontal disease is a form of chronic infection considered to contribute to the development of systemic inflammation. Although it is initiated by bacteria, its pathogenesis and progression are immune-mediated. The host overacts to infectious stimulation by secreting increased amounts of pro-inflammatory cytokines, such as IL-1β, TNF-α and IL-6, and matrix metalloproteinases (MMPs), which are tissue-destructive proteolytic enzymes (1). The locally produced pro-inflammatory mediators may enter the circulation and exert systemic effects. Increases in both the number of peripheral leukocytes and the levels of cytokines and acute-phase proteins have been found in patients with periodontal disease, but are not always significant (2,3). It has also been shown that this increase in leukocytes is aggravated by the severity and extent of the disease. Therapy may lead to a decrease in the number of leukocytes (4,5). Cytokine levels in the healthy systemic circulation are minimal and at times undetectable without the use of hypersensitive methodology (3). Pro-inflammatory mediators circulating in peripheral blood vessels may stimulate atherosclerosis or destabilize atherosclerotic plaque, thus increasing the likelihood of ischemic stroke (IS) (6). The aim of the present study was to compare cytokine concentrations in gingival fluid and serum between patients with IS and a control group matched for age and dental status. Materials and MethodsThe study subjects were 86 patients who were divided into two groups: IS patients and controls. The IS group included 50 randomly selected patients (18 women and 32 men; age range 38...

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“…35 Inflammatory cytokines levels in human plasma have been shown to increase as age increases, and monocytes, dendritic cells, and microglia produce more inflammatory cytokines in stimulated conditions. [38][39][40] In contrast, anti-inflammatory cytokine production decreases as age increases, which may be explained by aging-induced methylation that mediates the decrease in expression of genes of monocytes. 38,41 It is possible that as inflammation increases with age in women with and without endometriosis, the incremental risk associated with endometriosis in young women diminishes in the older women as age takes the dominated role in inflammation.…”

Section: Analysis 2: Hypercholesterolemia or Hypertension In Relationmentioning

confidence: 93%

Association Between Endometriosis and Hypercholesterolemia or Hypertension

Rich‐Edwards

Rimm

et al. 2017

Hypertension

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Abstract-An altered hormonal or chronic systemic inflammatory milieu characterizing endometriosis may result in a higher risk of hypercholesterolemia and hypertension. Conversely, elevated low-density lipoprotein in hypercholesterolemia and chronic systemic inflammation resulting from hypertension may increase the risk of endometriosis. We assessed the association of laparoscopically confirmed endometriosis with hypercholesterolemia and hypertension in a large prospective cohort study. In 1989, 116 430 registered female nurses aged 25 to 42 completed the baseline questionnaire and were followed for 20 years. Multivariable Cox proportional hazards models were applied. In 1989, there were 4244 women with laparoscopically confirmed endometriosis and 91 554 women without. After adjusting for demographic, anthropometric, family history, reproductive, dietary, and lifestyle risk factors prospectively, comparing women with laparoscopically confirmed endometriosis to women without, the relative risks were 1.25 (95% confidence interval, 1.21-1.30) for development of hypercholesterolemia and 1.14 (95% confidence interval, 1.09-1.18) for hypertension. Conversely, the relative risks of developing laparoscopically confirmed endometriosis were 1.22 (95% confidence interval, 1.15-1.31) comparing women with hypercholesterolemia to women without and 1.29 (95% confidence interval, 1.18-1.41) comparing women with hypertension to women without. The strength of associations of laparoscopically confirmed endometriosis with hypercholesterolemia or hypertension was strongest among women aged ≤40 and weakened as age increased (P values for interaction <0.001). We observed that ≈45% of the associations between endometriosis and hypercholesterolemia and hypertension could be accounted for by treatment factors after endometriosis diagnosis, including greater frequency of hysterectomy/oophorectomy and earlier age for this surgery. In this large cohort study, laparoscopically confirmed endometriosis was prospectively associated with increased risk of hypercholesterolemia and hypertension. Conversely, hypercholesterolemia and hypertension were prospectively associated with higher risk of laparoscopically confirmed endometriosis. process, which may be contributing to blood pressure elevation. 23 Hence the chronic systemic inflammation in endometriosis may predispose women with endometriosis to a higher risk of hypertension.In sum, women with endometriosis may have higher risk of hypercholesterolemia or hypertension, and women with hypertension or hypercholesterolemia may have a higher risk of endometriosis. We examined these hypotheses in the NHSII (Nurses' Health Study II), an ongoing prospective cohort study. Methods Study PopulationThe NHSII is a prospective cohort study with 116 430 registered female nurses who were 25 to 42 and resided in 14 of the United States at enrollment in 1989. At baseline, participants completed a detailed questionnaire and every 2 years thereafter completed follow-up questionnaires on the incidence of disease out...

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Age differences in cytokine expression under conditions of health using experimental pain models

Cited by 29 publications

References 49 publications

Age differences in salivary markers of inflammation in response to experimental pain: does venipuncture matter?

Age differences in salivary markers of inflammation in response to experimental pain: does venipuncture matter?

IL-1β, TNF-α, and IL-6 levels in gingival fluid and serum of patients with ischemic stroke

Association Between Endometriosis and Hypercholesterolemia or Hypertension

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