The clinical utility of three frailty measures in identifying HIV-associated neurocognitive disorders.

OBJECTIVE: Frailty measures vary widely and the optimal measure for predicting HIV-associated neurocognitive disorders (HAND) is unclear. DESIGN: A study was conducted to examine the clinical utility of three widely used frailty measures in identifying HIV-associated neurocognitive disorders. METHODS: The study involved 284 people with HIV (PWH) at least 50 years enrolled at UC San Diego's HIV Neurobehavioral Research Program. Frailty measurements included the Fried Phenotype, the Rockwood Frailty Index, and the Veterans Aging Cohort Study (VACS) Index. HAND was diagnosed according to Frascati criteria. ANOVAs examined differences in frailty severity across HAND conditions. ROC analyses evaluated sensitivity and specificity of each measure to detect symptomatic HAND [mild neurocognitive disorder (MND) and HIV-associated dementia (HAD)] from no HAND. RESULTS: Across all frailty measures, frailty was found to be higher in HAD compared with no HAND. For Fried and Rockwood (not VACS), frailty was significantly more severe in MND vs. no HAND and in HAD vs. ANI (asymptomatic neurocognitive impairment). For discriminating symptomatic HAND from no HAND, Fried was 37% sensitive and 92% specific, Rockwood was 85% sensitive and 43% specific, and VACS was 58% sensitive and 65% specific. CONCLUSION: These findings demonstrate that Fried and Rockwood outperform VACS in predicting HAND. However, ROC analyses suggest none of the indices had adequate predictive validity in detecting HAND. The results indicate that the combined use of the Rockwood and Fried indices may be an appropriate alternative.

Concurrent validity and reliability of at-home teleneuropsychological evaluations among people with and without HIV.

OBJECTIVE: To determine the reliability of teleneuropsychological (TNP) compared to in-person assessments (IPA) in people with HIV (PWH) and without HIV (HIV-). METHODS: Participants included 80 PWH (Mage = 58.7, SDage = 11.0) and 23 HIV- (Mage = 61.9, SDage = 16.7). Participants completed two comprehensive neuropsychological IPA before one TNP during the COVID-19 pandemic (March-December 2020). The neuropsychological tests included: Hopkins Verbal Learning Test-Revised (HVLT-R Total and Delayed Recall), Controlled Oral Word Association Test (COWAT; FAS-English or PMR-Spanish), Animal Fluency, Action (Verb) Fluency, Wechsler Adult Intelligence Scale 3rd Edition (WAIS-III) Symbol Search and Letter Number Sequencing, Stroop Color and Word Test, Paced Auditory Serial Addition Test (Channel 1), and Boston Naming Test. Total raw scores and sub-scores were used in analyses. In the total sample and by HIV status, test-retest reliability and performance-level differences were evaluated between the two consecutive IPA (i.e., IPA1 and IPA2), and mean in-person scores (IPA-M), and TNP. RESULTS: There were statistically significant test-retest correlations between IPA1 and IPA2 (r or ρ = .603-.883, ps < .001), and between IPA-M and TNP (r or ρ = .622-.958, ps < .001). In the total sample, significantly lower test-retest scores were found between IPA-M and TNP on the COWAT (PMR), Stroop Color and Word Test, WAIS-III Letter Number Sequencing, and HVLT-R Total Recall (ps < .05). Results were similar in PWH only. CONCLUSIONS: This study demonstrates reliability of TNP in PWH and HIV-. TNP assessments are a promising way to improve access to traditional neuropsychological services and maintain ongoing clinical research studies during the COVID-19 pandemic.

Plasma biomarkers of vascular dysfunction uniquely relate to a vascular-risk profile of neurocognitive deficits in virally-suppressed adults with HIV.

Objective: Chronic inflammation and vascular dysfunction (e.g., chronic endothelial activation) are related yet dissociable mechanisms of HIV-associated neurocognitive impairment (NCI), even among those on antiretroviral therapy (ART). However, how these mechanisms differentially contribute to domain-specific deficits in people with and without HIV (PWH, PWoH) is unclear. We empirically-derived profiles of NCI and examined relationships with peripheral inflammatory and vascular biomarkers. Methods: Participants were 84 virally-suppressed PWH and 126 PWoH who underwent neuropsychological testing and blood draw. Cluster analysis identified subgroups based on domain deficit scores. ANOVAs examined HIV serostatus and cluster group differences in composite plasma biomarker z-scores of inflammation (IL-6, CXCL10/IP-10, CCL2/MCP-1) and vascular injury (VCAM-1, ICAM-1, uPAR). Confirmatory regressions examined the interaction of HIV and biomarker z-scores on domain-specific T-scores, controlling for cardiovascular disease (CVD) risk and psychosocial factors. Results: Cluster analysis identified three groups: Unimpaired (n = 129), Learning/Recall (n = 52, isolated learning/recall deficits), Dysexecutive/Slow (n = 29, executive function, working memory, processing speed, and motor deficits). PWH had higher odds of Dysexecutive/Slow membership, which related to CVD risk and higher vascular dysfunction, but not inflammation, in PWH. Vascular biomarkers moderated adverse HIV effects on executive function, processing speed, and working memory such that PWH had lower T-scores only when vascular dysfunction was high. Conclusions: In PWH with controlled disease, peripheral markers of endothelial dysfunction and vascular permeability are selectively associated with an empirically-derived subgroup that exhibits domain deficits commonly impacted by cerebrovascular disease. Findings support the presence of a vascular NCI subgroup of PWH who may benefit from interventions that directly target the neurovascular unit.

Measuring the Frailty Phenotype and its Association with Cognition in Mid-Life and Older Age.

BACKGROUND: Frailty is directly linked to physical robustness and cognitive decline in older age. The Fried Frailty phenotype (FP) is a construct composed of five core symptoms that has been studied predominately in older age. There is little research contrasting the psychometric properties of the FP in mid-life versus older age. OBJECTIVE: We compared the psychometric properties of the FP in mid-life and older age and investigated relationships between the FP and cognition. METHODS: Frailty and neuropsychological assessments were completed on 361 adults, between 45 and 92 years of age, without primary neurological disorders. Confirmatory factor analysis was used to examine FP, indicated by Grip Strength, Gait Speed, Physical Activity, Fatigue, and Weight Loss. Measurement invariance was tested in mid-life (45-64 years) versus older age (≥65 years). Associations were examined between FP and language, executive functions, memory, processing speed, and visuospatial domains as well as a Generalized Cognition factor. Age was tested as a moderator of these associations. RESULTS: Weight Loss was a poor indicator of FP. Factor loadings were comparable across age groups; however, Fatigue was disproportionately higher among those in mid-life. FP was negatively associated with all cognitive domains and remained invariant across age groups. CONCLUSION: Results support the construct validity of the FP and document its stable associations with poorer cognition in middle and older life. Future research investigating central features of frailty earlier in life may offer avenues for developing targeted prevention measures and better characterization of individuals with elevated dementia risk.

Fatigue is associated with worse cognitive and everyday functioning in older persons with HIV.

OBJECTIVE: The aim of this study was to determine whether there are relationships between fatigue, cognition, and everyday functioning in older persons with and without HIV and to examine if associations remain after accounting for depression, anxiety, and sleep quality. METHODS: Sixty-nine persons with HIV (PWH) and 36 persons without HIV, aged 50-74 years, were recruited from ongoing studies at UC San Diego's HIV Neurobehavioral Research Program and from the community. Participants completed neuropsychological testing, a performance-based measure of everyday functioning, and self-report questionnaires of fatigue, depression, anxiety, sleep quality, and everyday functioning. Multivariable linear regressions and logistic regressions stratified by HIV serostatus were used to examine relationships between fatigue, cognition, and everyday functioning. Psychiatric symptoms and sleep quality were examined as covariates. RESULTS: In this cross-sectional study, PWH had significantly greater fatigue than the HIV-negative group (g  = 0.83; P < 0.01). When stratifying by HIV serostatus, greater fatigue was significantly associated with worse global cognition (ß = -0.56;P < 0.01) in PWH even when controlling for covariates;however, fatigue was not significantly associated with global cognition in persons without HIV. In PWH and when accounting for covariates, fatigue was also associated with greater risk of self-reported everyday functioning impairment [odds ratio (OR) = 1.66 for 10-point increase in fatigue, P  = 0.04] but not performance-based everyday functioning (P = 0.95). CONCLUSION: Fatigue is associated with cognition, particularly measures with a speeded component, and self-reported everyday functioning in older PWH. Findings suggest that fatigue is important to assess and consider in the context of aging with HIV.

Use of digital health technologies to examine subjective and objective sleep with next-day cognition and daily indicators of health in persons with and without HIV.

Most previous studies investigating sleep's association with health outcomes have relied on averaged sleep quality and laboratory-based health measures. This study examines the dynamic within-person relationships between subjective (Ecological Momentary Assessment) and objective sleep (actigraphy) on next-day cognition (subjective and objective), mood, and engagement in daily activities using linear mixed-effects regression modeling. Participants included 94 individuals (59 people with HIV, 35 HIV-) aged 50-74, assessed daily for 14 consecutive days/nights. Subjective and objective sleep were well correlated and were both associated with subjective ratings of cognition, but not objective cognition. Worse subjective sleep was associated with next-day lower happiness and higher depressed mood, and more pain, but was not related to next-day daily activities. Objective sleep was associated with next-day depressed mood and feelings of worry, and was positively associated with next-day television watching. Results provide evidence to support the utility of real-time assessment for sleep and functional outcomes that may lead to potential personalized interventions for individuals with and without HIV.

Frailty Syndrome Is Associated with Poorer Self-Reported Sleep Quality Among Older Persons with Human Immunodeficiency Virus.

Older people with HIV (PWH) experience heightened risk for the acquisition of cumulative, multisystem decline, that is, frailty syndrome. Frailty relates to poorer sleep quality in the general older adult population; however, this association has yet to be explored among PWH. A cross-sectional analysis of 285 PWH ≥50 years of age (mean age 60.5 ± 7.0) examined the relationship between frailty (Fried frailty phenotype) and self-reported sleep quality [Pittsburgh Sleep Quality Index (PSQI)]. Three separate multivariable linear regression models examined global PSQI as a function of (1) frailty phenotype, (2) total number of frailty symptoms, or (3) specific individual frailty symptoms. Models covaried for demographic and biopsychosocial risk factors, including age, sex, race/ethnicity, education, premorbid verbal IQ estimate, current depressive symptoms, and diagnosis of a substance abuse disorder. Compared to nonfrail (B = 0.151; p = .021) and prefrail (B = 0.144; p = .021), frail phenotype was related to poorer sleep quality (increased global PSQI; F(5,278) = 11.34, p < .001; R2 = 0.17). Increased number of frailty symptoms (B = 0.144; p = .019; F(4,276) = 12.719, p < .001; R2 = 0.16) and exhaustion was associated with increased global PSQI scores (B = 0.218, p < .001; F(6,247) = 10.436, p < .001; R2 = 0.19). In all models, older age, female sex, and elevated current depressive symptoms were associated with poorer sleep quality. In older PWH, greater frailty symptoms related to poorer sleep quality, independent of psychosocial risk factors for poor sleep. Frailty and poor sleep individually have adverse effects on health and everyday functioning; thus, establishing this association may better aid providers to screen for and treat problems with sleep quality and/or frailty among PWH.

Loneliness, Risky Beliefs and Intentions about Practicing Safer Sex among Methamphetamine Dependent Individuals.

BACKGROUND: Methamphetamine use is a known predictor of riskier sexual behaviors, which can have important public health implications (e.g., HIV-transmission risk). Loneliness also is associated with riskier sexual behaviors, though the relationship between loneliness and beliefs and/or intentions to practice safer sex has not been examined among people dependent on methamphetamine. MATERIALS AND METHODS: Individuals who met DSM-IV criteria for lifetime methamphetamine dependence and current (≤ 18-months) methamphetamine abuse or dependence (METH+ n = 56) were compared to those without severity and recency of methamphetamine use (METH- n = 59). These groups did not differ on social network size or proportion of people with HIV (∼58% HIV+). Participants completed the NIH Toolbox Loneliness Scale and the Sexual Risks Scale's "Norms" and "Intentions" subscales. RESULTS: METH+ individuals were significantly lonelier than METH- controls (t(113) = 2.45, p = .02). Methamphetamine dependence remained significantly associated with greater loneliness, after controlling for HIV status and other relevant covariates (e.g., neurocognitive impairment, history of mood disorder, social network size; F = 3.70, Adjusted R2 = 0.18, p = .0009). Loneliness, above and beyond the aforementioned covariates, was significantly associated with riskier beliefs and intentions to practice safer sex among METH+, but not METH-, individuals (ß = 2.92, p = .02). CONCLUSIONS: Loneliness is prevalent among individuals dependent on methamphetamine, and is uniquely associated with riskier beliefs and intentions regarding practicing safer sex. Findings may aid in identifying individuals at-risk of engaging in riskier sexual behaviors and guide risk prevention strategies.

Daily Cannabis Use is Associated With Lower CNS Inflammation in People With HIV.

OBJECTIVE: Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis's anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH. METHODS: 263 individuals were categorized into four groups: HIV- non-cannabis users (n = 65), HIV+ non-cannabis users (n = 105), HIV+ moderate cannabis users (n = 62), and HIV+ daily cannabis users (n = 31). Differences in pro-inflammatory biomarkers (IL-6, MCP-1/CCL2, IP-10/CXCL10, sCD14, sTNFR-II, TNF-α) by study group were determined by Kruskal-Wallis tests. Multivariable linear regressions examined relationships between biomarkers and seven cognitive domains, adjusting for age, sex/gender, race, education, and current CD4 count. RESULTS: HIV+ daily cannabis users showed lower MCP-1 and IP-10 levels in CSF compared to HIV+ non-cannabis users (p = .015; p = .039) and were similar to HIV- non-cannabis users. Plasma biomarkers showed no differences by cannabis use. Among PWH, lower CSF MCP-1 and lower CSF IP-10 were associated with better learning performance (all ps < .05). CONCLUSIONS: Current daily cannabis use was associated with lower levels of pro-inflammatory chemokines implicated in HIV pathogenesis and these chemokines were linked to the cognitive domain of learning which is commonly impaired in PWH. Cannabinoid-related reductions of MCP-1 and IP-10, if confirmed, suggest a role for medicinal cannabis in the mitigation of persistent inflammation and cognitive impacts of HIV.

Social Isolation Is Linked to Inflammation in Aging People With HIV and Uninfected Individuals.

BACKGROUND: Even in the era of suppressive antiretroviral therapy, people with HIV (PWH) suffer greater exposure to inflammation than their uninfected peers. Although poor social support and social isolation have been linked to systemic inflammation in the general population, it is not known whether this is true also among PWH. METHODS: People with and without HIV infection were enrolled in a community-based, single-center study. Primary predictors were the Medical Outcomes Study Social Support Survey, and outcomes were a panel of inflammatory biomarkers (ICAM-1, MCP-1, IL-6, IL-8, IP-10, C-reactive protein, D-dimer, VEGF, sCD14, and uPAR) in blood plasma and cerebrospinal fluid (CSF). RESULTS: PWH had worse positive social support (P = 0.0138) and affectionate support (P = 0.0078) than did HIV- individuals. A factor analysis was used to group the biomarkers into related categories separately for each fluid. Levels of 3 of the 4 plasma factors were significantly higher in PWH than HIV- (ps = 0.007, 0.001, and 0.0005, respectively). Levels of 1 of the 3 CSF factors also were significantly higher in PWH than HIV- (P = 0.0194). In the combined PWH and HIV- cohort, poorer social support was associated with higher levels of a factor in plasma loading on MCP-1, IL-8, and VEGF (P = 0.020) and with a CSF factor loading on MCP-1 and IL-6 (P = 0.006). CONCLUSION: These results suggest that enhancing social support might be an intervention to reduce inflammation and its associated adverse outcomes among PWH.

Brief Report: Frailty and HIV Disease Severity Synergistically Increase Risk of HIV-Associated Neurocognitive Disorders.

BACKGROUND: Frailty disproportionally affects people with HIV (PWH) and increased frailty in this already vulnerable population is associated with worse neurocognitive functioning. Whether frailty interacts with current and modifiable markers of HIV disease severity to synergistically increase risk for HIV-associated neurocognitive disorders (HAND), however, is unknown and important for informing the clinical care of aging PWH. SETTING: UC San Diego's HIV Neurobehavioral Research Program. METHODS: Participants were 178 PWH evaluated between 2014 and 2019. HIV disease severity was measured by current CD4 count and plasma HIV RNA. HAND diagnoses were made according to the Frascati criteria using a 7-domain neuropsychological battery, and the Fried phenotype criteria were used to assess frailty syndrome (0-5 symptoms). The independent and interactive effects of frailty and current HIV disease severity (ie, CD4 count and plasma HIV RNA) on HAND were examined using multiple logistic regressions. RESULTS: There was an interaction between CD4 count and frailty on HAND. Simple slopes showed that CD4 count and the likelihood of HAND were negatively associated at >1.25 symptoms of frailty, and conversely, frailty and HAND were negatively associated at 642 or less cells/mm. There were no significant independent or interactive effects of plasma HIV RNA and frailty on the likelihood of HAND. CONCLUSIONS: In addition to monitoring CD4 count, assessing for frailty may be critical in older adults with HIV to potentially mitigate poor neurobehavioral outcomes. Longitudinal follow-up studies are needed to determine the directionality of these findings.

Lifetime Methamphetamine Use Disorder and Reported Sleep Quality in Adults Living with HIV.

This study evaluated whether a history of lifetime methamphetamine (MA) use disorder increases risk for poor sleep quality in people with or without HIV infection (HIV+/HIV-). Participants (n = 313) were stratified into four groups based on HIV status and lifetime MA use disorder diagnosis [HIV+/MA+ (n = 84); HIV+/MA- (n = 141); HIV-/MA+ (n = 16); and HIV-/MA- (n = 72)] and compared on global sleep outcomes using the Pittsburgh Sleep Quality Index (PSQI). Significant differences on global sleep were observed between HIV+/MA+ and HIV+/MA- groups, but not between the HIV- groups. Follow-up multiple regression analyses within the HIV+ subgroups examined global sleep scores as a function of MA status and clinical covariates, including those related to HIV disease and demographics. HIV+ individuals with a history of MA use disorder evidenced significantly poorer sleep quality and were more likely to be classified as problematic sleepers than those without a lifetime disorder. This was independent of depressed mood, body mass index, and viral suppression while on treatment. Poorer reported sleep quality among HIV+/MA+ was associated also with multiple adverse functional outcomes, including greater objective cognitive impairment, unemployment, clinical ratings of functional impairment, and self-reported cognitive difficulties, decreased independence in activities of daily living, and poorer overall life quality. Interventions to avoid or curtail MA use in HIV+ individuals may help protect sleep quality and improve functioning.

Social support moderates D-dimer and self-rated successful aging within people with HIV and older adults.

Many factors can influence perceptions of successful aging (SA), including social isolation and poor physical health. We hypothesized that social support attenuates the negative effect of plasma D-dimer, a correlate of HIV and aging, on SA. Participants included 230 adults (134 people with HIV; PWH, 96 HIV-), ages 36-65, segregated into age cohorts with up to 5 yearly visits. Multilevel modeling examined longitudinal within-person associations between D-dimer, social support, and SA. Social support moderated the relationship between D-dimer and SA and was significant among PWH and older individuals (ages 56-65), but not HIV- or younger cohorts. This association was significant only at extreme levels of social support, with significant decreases in social support potentiating the negative impact of D-dimer on SA and significant increases in social support facilitating increased SA. Despite declining health, high social support may improve SA in PWH and older adults, and low support may be especially problematic for older adults.

Neuropsychological correlates of subjective fatigue in non-demented older adults and the moderating effect of physical activity.

This study examined the association between self-reported fatigue and neuropsychological performance in 167 middle-aged and older (age range: 50-91 years) adults without dementia. Participants completed the Fatigue Symptom Inventory, a comprehensive neuropsychological evaluation, and frailty assessment. Higher levels of fatigue were significantly associated with poorer attention/information processing, executive functioning, and psychomotor speed, even after controlling for depression, sleep quality, physical weakness, and other covariates. Participants endorsing moderate-severe fatigue faced higher odds (OR = 6.6, 95% CI = 1.1, 39.1) of exhibiting clinical attention/information processing impairments than those without. Moderation analyses showed that fatigue was related to select cognitive deficits among those reporting mean or lower levels of activity, but not high levels. These findings highlight fatigue as an important clinical marker of select cognitive deficits in non-demented older adults that is distinct from the common confounding conditions examined in this study. High levels of physical activity may buffer this relationship.

Pre-frailty predicts cognitive decline at 2-year follow-up in persons living with HIV.

Both HIV disease and frailty syndrome are risk factors for neurocognitive impairment. Longitudinal research among individuals of the general population suggests that frailty predicts future cognitive decline; however, there is limited evidence for these longitudinal relationships among people living with HIV (PLWH). The current study evaluated and compared rates of cognitive decline over 2 years among HIV serostatus and frailty status groups. Participants included 50 PLWH and 60 HIV-uninfected (HIV-) participants who were evaluated at baseline and 2-year follow-up visits. Baseline frailty status (non-frail, pre-frail, and frail) was determined using fried frailty phenotype criteria. Neurocognitive functioning was measured using practice-effect corrected scaled scores derived from a comprehensive neuropsychological battery covering seven cognitive domains. Repeated measures analysis was used to estimate rates of global and domain-specific cognitive change from baseline to 2-year follow-up among each of six HIV/frailty status groups. Among PLWH, the pre-frail group demonstrated consistent declines in global cognitive functioning (B = - 0.029, p = 0.034), processing speed (B = - 0.047, p = 0.031), and motor functioning (B = - 0.048, p = 0.038). Among HIV- participants, pre-frail individuals also declined in global cognitive functioning and processing speed (ps ≤ 0.05). HIV- non-frail participants also declined in the cognitive domains of learning, delayed recall, and motor functioning; however, these declines appeared to be driven by relatively higher baseline scores among this group. Notably, 38% of PLWH changed in frailty status from baseline to follow-up, and those with stable pre-frailty demonstrated higher likelihood for cognitive decline; change in depressive symptoms did not relate to change in frailty status. Current findings highlight pre-frailty as an important clinical syndrome that may be predictive of cognitive decline among PLWH. Interventions to prevent or reduce frailty among vulnerable PLWH are needed to maintain optimal cognitive health.

Sleep quality mediates the relationship between frailty and cognitive dysfunction in non-demented middle aged to older adults.

ABSTRACTObjectives:Frailty is associated with cognitive decline in older adults. However, the mechanisms explaining this relationship are poorly understood. We hypothesized that sleep quality may mediate the relationship between frailty and cognition. PARTICIPANTS: 154 participants aged between 50-90 years (mean = 69.1 years, SD = 9.2 years) from the McKnight Brain Registry were included. MEASUREMENTS: Participants underwent a full neuropsychological evaluation, frailty and subjective sleep quality assessments. Direct relationships between frailty and cognitive function were assessed using linear regression models. Statistical mediation of these relationships by sleep quality was assessed using nonparametric bootstrapping procedures. RESULTS: Frailty severity predicted weaker executive function (B = -2.77, ß = -0.30, 95% CI = -4.05 - -1.29) and processing speed (B = -1.57, ß = -0.17, 95% CI = -3.10 - -0.16). Poor sleep quality predicted poorer executive function (B = -0.47, ß = -0.21, 95% CI = -0.79 - -0.08), processing speed (B = -0.64, ß = -0.28, 95% CI = -0.98 - -0.31), learning (B = -0.42, ß = -0.19, 95% CI = -0.76 - -0.05) and delayed recall (B = -0.41, ß = -0.16, 95% CI = -0.80 - -0.31). Poor sleep quality mediated the relationships between frailty severity and executive function (B = -0.66, ß = -0.07, 95% CI = -1.48 - -0.39), learning (B = -0.85, ß = -0.07, 95% CI = -1.85 - -0.12), delayed recall (B = -0.47, ß = -0.08, 95% CI = -2.12 - -0.39) and processing speed (B = -0.90, ß = -0.09, 95% CI = -1.85 - -0.20). CONCLUSIONS: Relationships between frailty severity and several cognitive outcomes were significantly mediated by poor sleep quality. Interventions to improve sleep quality may be promising avenues to prevent cognitive decline in frail older adults.

Regulation of the macrophage oxytocin receptor in response to inflammation.

It has been demonstrated that the neuropeptide oxytocin (OT) attenuates oxidative stress and inflammation in macrophages. In the current study, we examined the role of inflammation on the expression of the oxytocin receptor (OXTR). We hypothesized that OXTR expression is increased during the inflammation through a nuclear factor-κB (NF-κB)-mediated pathway, thus responding as an acute-phase protein. Inflammation was induced by treating macrophages (human primary, THP-1, and murine) with lipopolysaccharide (LPS) and monitored by expression of IL-6. Expression of OXTR and vasopressin receptors was assessed by qPCR, and OXTR expression was confirmed by immunoblotting. Inflammation upregulated OXTR transcription 10- to 250-fold relative to control in THP-1 and human primary macrophages and increased OXTR protein expression. In contrast, vasopressin receptor-2 mRNA expression was reduced following LPS treatment. Blocking NF-κB activation prevented the increase in OXTR transcription. OT treatment of control cells and LPS-treated cells increased ERK1/2 phosphorylation, demonstrating activation of the OXTR/Gαq/11 signaling pathway. OT activation of OXTR reduced secretion of IL-6 in LPS-activated macrophages. Collectively, these findings suggest that OXTR is an acute-phase protein and that its increased expression is regulated by NF-κB and functions to attenuate cellular inflammatory responses in macrophages.