Circulating mediators of inflammation and immune activation in AIDS-related non-Hodgkin lymphoma

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods: This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed beadbased immunoassays. Results: A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions: These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease. © 2014 Nolen et al

Sleep loss activates cellular inflammation and signal transducer and activator of transcription (STAT) family proteins in humans

Sleep disturbance and short sleep duration are associated with inflammation and related disorders including cardiovascular disease, arthritis, diabetes mellitus, and certain cancers. This study was undertaken to test the effects of experimental sleep loss on spontaneous cellular inflammation and activation of signal transducer and activator of transcription (STAT) family proteins, which together promote an inflammatory microenvironment. In 24 healthy adults (16 females; 8 males), spontaneous production of IL-6 and TNF-α in monocytes and spontaneous intranuclear expression of activated STAT1, STAT3, and STAT5 in peripheral blood mononuclear cells (PBMC), monocyte-, and lymphocyte populations were measured in the morning after uninterrupted baseline sleep, partial sleep deprivation (PSD, sleep period from 3a.m. to 7a.m.), and recovery sleep. Relative to baseline, spontaneous monocytic expression of IL-6 and TNF-α was significantly greater after PSD (P<0.02) and after recovery sleep (P<0.01). Relative to baseline, spontaneous monocytic expression of activated STAT1 and STAT5 was significantly greater after recovery sleep (P<0.007 and P<0.02, respectively) but not STAT3 (P=0.09). No changes in STAT1, STAT3, or STAT5 were found in lymphocyte populations. Sleep loss induces activation of spontaneous cellular innate immunity and of STAT family proteins, which together map the dynamics of sleep loss on the molecular signaling pathways that regulate inflammatory and other immune responses. Treatments that target short sleep duration have the potential to constrain inflammation and reduce the risk for inflammatory disorders and some cancers in humans

Opioid treatment of experimental pain activates nuclear factor-κB.

ObjectiveTo determine the independent and combined effects of pain and opioids on the activation of an early marker of inflammation, nuclear factor-κB (NF-κB).DesignNF-κB activation was compared within-subjects following four randomly ordered experimental sessions of opioid-only (intravenous fentanyl 1 μg/kg), painonly (cold-pressor), opioid + pain, and a resting condition.SettingUniversity General Clinical Research Center.ParticipantsTwenty-one (11 female) healthy controls.InterventionsFollowing exposure to treatment (fentanyl administration and/or cold-pressor pain), blood samples for NF-κB analysis were obtained.Main outcome measuresIntracellular levels of activated NF-κB, in unstimulated and stimulated peripheral blood mononuclear cells at 15 and 30 minutes.ResultsNeither pain nor opioid administration alone effected NF-κB levels in cell populations; however, the combination of treatments induced significant increases of NF-κB in stimulated peripheral blood mononuclear cell, lymphocytes, and monocytes.ConclusionsThe combination of acute pain with opioids, as occurs in clinical situations, activates a key transcription factor involved in proinflammatory responses

In patients with stable heart failure, soluble TNF-receptor 2 is associated with increased risk for depressive symptoms.

ObjectivesResearchers have proposed biological (inflammation) and psychological (depression) factors as potential mechanisms for poorer outcomes and readmissions in heart failure (HF) patients. However, studies investigating the link between inflammation and depressive symptoms in these patients are few. We examined the relationships between levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and soluble tumor necrosis factor receptor 2 (sTNR2) and depressive symptoms in HF outpatients.Method55 patients (74.5% men; 60% Whites; mean age 71.6 ± 11.3 years) with New York Heart Association Class II, III, or IV HF (49%, 47%, and 4%, respectively) and mean ejection fraction (EF) 29.9 ± 7.1% completed the Patient Health Questionnaire (PHQ)-9 as a measure of depressive symptoms. We also obtained height, weight, and CRP, IL-6, and sTNFR2 levels. We used multivariate regressions to assess the predictive value of PHQ-9 scores on each inflammatory marker.Results22 (40%) participants reported depressive symptoms (PHQ-9 score ≥ 5). After controlling for age, gender, body mass index, HF etiology, EF, and statin use, we found significant relationships between levels of both sTNFR2 (β = .35, p = .01) and IL-6 (β = .30, p = .04), but not CRP (β = -.96, p = .52), and depression scores.ConclusionOur findings add to a growing body of evidence supporting the proposition that heightened inflammation explains the effect depression has on HF. Health care providers should screen for depression in HF patients, as they may be at higher risk of augmented inflammation and poor outcomes

In patients with stable heart failure, soluble TNF-receptor 2 is associated with increased risk for depressive symptoms.

ObjectivesResearchers have proposed biological (inflammation) and psychological (depression) factors as potential mechanisms for poorer outcomes and readmissions in heart failure (HF) patients. However, studies investigating the link between inflammation and depressive symptoms in these patients are few. We examined the relationships between levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and soluble tumor necrosis factor receptor 2 (sTNR2) and depressive symptoms in HF outpatients.Method55 patients (74.5% men; 60% Whites; mean age 71.6 ± 11.3 years) with New York Heart Association Class II, III, or IV HF (49%, 47%, and 4%, respectively) and mean ejection fraction (EF) 29.9 ± 7.1% completed the Patient Health Questionnaire (PHQ)-9 as a measure of depressive symptoms. We also obtained height, weight, and CRP, IL-6, and sTNFR2 levels. We used multivariate regressions to assess the predictive value of PHQ-9 scores on each inflammatory marker.Results22 (40%) participants reported depressive symptoms (PHQ-9 score ≥ 5). After controlling for age, gender, body mass index, HF etiology, EF, and statin use, we found significant relationships between levels of both sTNFR2 (β = .35, p = .01) and IL-6 (β = .30, p = .04), but not CRP (β = -.96, p = .52), and depression scores.ConclusionOur findings add to a growing body of evidence supporting the proposition that heightened inflammation explains the effect depression has on HF. Health care providers should screen for depression in HF patients, as they may be at higher risk of augmented inflammation and poor outcomes