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Objective: Inflammation is increasingly understood as playing an important role in type 2 diabetes mellitus (T2D) development. A critical mechanism of the inflammatory cascade in developing T2D is nuclear factor-kappa B (NF-kB) activation. As immunoglobulin free light chains (FLC) could be a biomarker of activation of NF-kB, we measured FLC in patients with T2D., Subjects: The age range of the 77 patients with T2D and the 75 healthy control participants were 45-87 years (median 60) and 25-72 years (median 51), respectively., Methods: Serum FLC kappa and lambda were assayed by a competitive-inhibition multiplex Luminex assay., Results: The concentration of circulating FLC the kappa/lambda ratio was lower in patients with T2D than in healthy volunteers. The area under the receiver operating curve (ROC-AUC) of the FLC kappa/lambda ratio showed the largest ROC-AUC compared with other FLC variables and hemoglobin A1c (HbA1c). The diagnostic performance for distinguishing between T2D and healthy control was a sensitivity of 0.96 and a specificity of 1. The odds ratio was 0.000018., Conclusions: These results suggest that FLC kappa/lambda may be more specific and sensitive for the diagnosis of T2D than HbA1c, and thus represents a potentially promising biomarker of inflammation.

Illness is often accompanied by perceived cognitive sluggishness, a symptom that may stem from immune system activation. The current study used electroencephalography (EEG) to assess how inflammation affected three different distinct attentional processes: alerting, orienting and executive control. In a double-blinded placebo-controlled within-subjects design (20 healthy males, mean age = 24.5, SD = 3.4), Salmonella typhoid vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur) was used to induce transient mild inflammation, while a saline injection served as a placebo-control. Participants completed the Attention Network Test with concurrent EEG recorded 6 h post-injection. Analyses focused on behavioral task performance and on modulation of oscillatory EEG activity in the alpha band (9-12 Hz) for alerting as well as orienting attention and frontal theta band (4-8 Hz) for executive control. Vaccination induced mild systemic inflammation, as assessed by interleukin-6 (IL-6) levels. While no behavioral task performance differences between the inflammation and placebo condition were evident, inflammation caused significant alterations to task-related brain activity. Specifically, inflammation produced greater cue-induced suppression of alpha power in the alerting aspect of attention and individual variation in the inflammatory response was significantly correlated with the degree of alpha power suppression. Notably, inflammation did not affect orienting (i.e., alpha lateralization) or executive control (i.e., frontal theta activity). These results reveal a unique neurophysiological sensitivity to acute mild inflammation of the neural network that underpins attentional alerting functions. Observed in the absence of performance decrements, these novel findings suggest that acute inflammation requires individuals to exert greater cognitive effort when preparing for a task in order to maintain adequate behavioral performance., (Copyright © 2019. Published by Elsevier Inc.)

The established link between loneliness and poor health outcomes may stem from aberrant inflammatory regulation. The present study tested whether loneliness predicted the inflammatory response to a standardised in vivo immune challenge. Using a within-subjects double blind placebo-controlled design, 40 healthy men (mean age = 25, SD = 5) received a Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur, UK) and placebo (saline) on two separate occasions. Loneliness was assessed using the R-UCLA loneliness scale. Regression analyses showed that those that reported feeling more lonely exhibited an elevated interleukin-6 response (β = 0.564, 95% confidence interval [0.003, 0.042], p < .05). This association withstood adjustment for potentially confounding variables, including age, sleep quality, socio-emotional factors, and health factors. The present findings are in line with evidence that loneliness may shift immune system responsivity, suggesting a potential biobehavioural pathway linking loneliness to impaired health., (Copyright © 2019. Published by Elsevier Inc.)

Problem: Pre-eclampsia (PE) is a leading cause of maternal and foetal morbidity worldwide. Given the implication of immune mechanisms, we compared markers of humoral immunity in PE and their relationship to circulating markers of inflammation, angiogenic factors, and renal function., Method of Study: Serum samples from 88 previously healthy women admitted to hospital with PE and 107 healthy pregnant controls at term were analysed for serum immunoglobulins (Ig), including IgG subclasses and free light chain (sFLC) levels, beta-2 microglobulin (B2-M), high-sensitivity C-reactive protein (HS-CRP), albumin, complement proteins (C3 & C4), creatinine, cystatin-C and the ratio of soluble fms-like tyrosine kinase-1 (sFLT-1) and placental growth factor (PlGF)., Results: Compared to the controls, women with PE had significantly reduced renal function, serum IgG (subclass 1 & 3), albumin, and C4 levels, whilst concentrations of total sFLC, HS-CRP, B2-M, and sFLT-1:PlGF were raised. On multivariable analysis, sFLT-1:PlGF ratio (P < 0.001), sFLC (P < 0.001) and IgG1 (P < 0.024) were found to be independently associated with PE, after accounting for renal function, patient age, BMI, ethnicity, and parity. B2-M and sFLT-1:PlGF had comparable diagnostic association with PE (P = 0.184), and correlated strongly with each other (ρ = 0.588, P < 0.001) as well as with renal function and adverse clinical outcome., Conclusion: We describe for the first time that PE is independently associated with activation of the humoral immune system independent of deranged kidney function and angiogenic markers. The role of B2-M as a potential predictive marker of PE remains to be determined., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The ability to adequately interpret the mental state of another person is key to complex human social interaction. Recent evidence suggests that this ability, considered a hallmark of 'theory of mind' (ToM), becomes impaired by inflammation. However, extant supportive empirical evidence is based on experiments that induce not only inflammation but also induce discomfort and sickness, factors that could also account for temporary social impairment. Hence, an experimental inflammation manipulation was applied that avoided this confound, isolating effects of inflammation and social interaction. Forty healthy male participants (mean age = 25, SD = 5 years) participated in this double-blind placebo-controlled crossover trial. Inflammation was induced using Salmonella Typhi vaccination (0.025 mg; Typhim Vi, Sanofi Pasteur, UK); saline-injection was used as a control. About 6 h 30 m after injection in each condition, participants completed the Reading the Mind in the Eyes Test (RMET), a validated test for assessing how well the mental states of others can be inferred through observation of the eyes region of the face. Vaccination induced systemic inflammation, elevating IL-6 by +419% (p < .001), without fever, sickness symptoms (e.g., nausea, light-headedness), or mood changes (all p's > .21). Importantly, compared to placebo, vaccination significantly reduced RMET accuracy (p < .05). RMET stimuli selected on valence (positive, negative, neutral) provided no evidence of a selective impact of treatment. By utilizing an inflammation-induction procedure that avoided concurrent sicknesses or symptoms in a double-blinded design, the present study provides further support for the hypothesis that immune activation impairs ToM. Such impairment may provide a mechanistic link explaining social-cognitive deficits in psychopathologies that exhibit low-grade inflammation, such as major depression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Elevated inflammatory levels are linked to poorer cognition, but experimental confirmation is lacking. This report examined associations between cognitive performance and inflammation induced by exercise and vaccination. Thirty-six (exercise N = 18, vaccination N = 18) healthy males completed a paced auditory serial addition test (PASAT), which is a multifaceted measure of cognitive function. The task was completed in placebo and elevated inflammation states. Improvements in PASAT performance were related to inflammation. In the exercise study, IL-6 during the first PASAT negatively correlated with PASAT improvement (p = .022). In the vaccination study, increases in C-reactive protein between PASATs correlated with reduced PASAT improvement (p < .001). Inflammation was linked to reduced improvements in cognitive performance. Further research should identify the specific cognitive functions affects and the underlying mechanisms., (© 2014 Society for Psychophysiological Research.)

Inflammation is associated with poorer vascular function, with evidence to suggest that inflammation can also impair the vascular responses to mental stress. This study examined the effects of vaccine-induced inflammation on vascular responses to mental stress in healthy participants. Eighteen male participants completed two stress sessions: an inflammation condition having received a typhoid vaccination and a control (non-inflamed) condition. Tumor necrosis factor-alpha and interleukin-6 (p's<.001) increased following vaccination, confirming modest increases in inflammation. Mental stress increased blood flow, blood pressure, heart rate, and cardiac output in both conditions (all p's<.001), but the blood flow response to stress was attenuated having received the vaccination compared to the control condition (p's<.05). These results further implicate the interaction between inflammation and the vasculature as a mechanism through which stress may trigger myocardial infarction., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Mental stress is considered to be a trigger for acute myocardial infarction (MI), with inflammation thought to provide a mechanism. Inflammation is reciprocally linked to oxidative stress, which has also been implicated in MI. The purpose of this study was to assess the effects of experimentally-induced inflammation on the oxidative stress response to mental stress in healthy participants., Methods: Healthy males undertook one of two inflammatory stimuli: typhoid vaccination (Vaccination paradigm, N=17) or eccentric exercise (Eccentric exercise paradigm, N=17). All participants completed a mental arithmetic stress task twice (within-subject design): 6h after the inflammatory stimulus, and during a control non-inflammation condition. Blood samples were taken before, immediately and 30min after the stress task. Plasma was assessed for interleukin-6 (IL-6), protein carbonyls (PC), lipid hydroperoxides (LOOH), total antioxidant capacity (TAC) and nitric oxide metabolites (NOx)., Results: Vaccination paradigm: IL-6, PC and NOx were significantly higher in the vaccination condition, relative to the control condition (p<.05). PC, TAC, LOOH and NOx were unchanged in response to mental stress in both the vaccination and control conditions. Eccentric Exercise paradigm: IL-6 and TAC were significantly higher in the eccentric exercise condition (p<.05), relative to the control condition. PC, TAC and NOx were unchanged in response to mental stress in both the eccentric exercise and control conditions., Conclusions: Two different inflammatory paradigms were successful in increasing selective plasma markers of inflammation and oxidative stress prior to a mental stress task. However, experimentally induced transient inflammation had no impact on mental stress-induced changes in plasma LOOH, PC, TAC or NOx in young healthy participants., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The Salmonella typhi vaccination induces transient increases in inflammatory-responsive cytokines and molecules. For instance, it causes small, mild increases in interleukin-6 (IL-6) within a few hours and C-reactive protein (CRP) within 24h. No study has charted either the time course of the inflammatory response to this vaccine or any associated changes in mood, physical symptoms, and cardiac function. In a blinded crossover experimental design, eight participants received the S. typhi vaccine (vaccination condition) and a saline (control condition) injection on two separate days, at least one week apart. Blood samples and mood ratings were collected at 0, 4, 5, 6, 7, 8 and 24h post-injection, physical symptoms and pain were assessed at 4-8 and 24h post-injection, and cardiovascular function was recorded until 8h post-injection. Repeated measures analyses of variance and polynomial trend analyses compared the timecourse of the response patterns between the two conditions. Whereas there were no temporal changes in the control condition, the vaccination increased granulocytes, IL-6, TNF-α, and CRP (all p's<.05). Specifically, the granulocytes, IL-6 and TNF-α peaked after 6-8h while CRP peaked after 24h. This vaccine-induced mild inflammatory response was not accompanied by any changes in mood or cardiovascular activity. We also found that participants tended to report more pain in the injected limb in the vaccination condition (p<.07). In sum, our study charted the timecourse of key inflammatory-responsive markers following S. typhi vaccination and identified the timing of their modest peaks. It is worth noting that changes in these markers were not accompanied by any notable changes in mood or cardiovascular activity, and thus the S. typhi vaccination is a suitable method to induce increases in inflammatory-responsive markers, without altering mood or cardiovascular parameters., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Traditionally, free light chains (FLCs) are used as key serum biomarkers in the diagnosis and monitoring of plasma cell malignancies, but polyclonal FLCs can also be used as an accurate real-time indicator of immune-activation and inflammation. The primary aim of the present study was to assess the effects of exercise training status on serum FLCs in older adults, and secondly, to examine if training status moderated serum FLC responses to acute exercise. Kappa and lambda serum FLC levels were measured in 45 healthy older adults (aged ≥ 60 years) who were either sedentary, physically active or endurance trained. FLCs were measured at baseline and in response to an acute bout of submaximal exercise. The endurance trained group had significantly lower levels of kappa and lambda serum FLCs compared with physically active or sedentary elderly adults; these effects were independent of age, BMI and renal function. There was no significant difference in whole immunoglobulins between groups. Exercise training status had no effect on serum FLC responses to acute exercise, which were marginal. In conclusion, endurance training was associated with lower FLC levels compared with less physically active individuals. These findings suggest that long-term endurance training may be beneficial in reducing basal inflammation in older adults as well as elevated FLCs present in inflammatory and autoimmune conditions, often associated with ageing. FLCs may serve as a useful biomarker for monitoring the efficacy of exercise intervention studies in healthy and clinical populations. [ABSTRACT FROM AUTHOR]

In this study, we measured immunoglobulin free light chains (FLC), a biomarker of inflammation in the sera of patients with heart failure due to myocarditis. FLC kappa and FLC lambda were assayed in stored serum samples from patients with heart failure with myocarditis from the US myocarditis treatment trial by a competitive-inhibition multiplex Luminex® assay. The median concentration of circulating FLC kappa/lambda ratio was significantly lower in the sera from patients with heart failure with myocarditis than in healthy controls, and FLC kappa/lambda ratio had good diagnostic ability for identification of heart failure with myocarditis. Further, FLC kappa/lambda ratio was an independent prognostic factor for overall survival, and allowed creation of three prognostic groups by combining with N-terminal pro-B-type natriuretic peptide. This study suggests that FLC kappa/lambda ratio is a promising biomarker of heart failure with myocarditis. • Immunoglobulin free light chains (FLC) are biomarkers of inflammation. • FLC kappa/lambda ratio (K/L) is lower in myocarditis than healthy controls. • FLC K/L ratio is an independent prognostic factor for overall survival in myocarditis. [ABSTRACT FROM AUTHOR]