Long-Term Suppressive Combined Antiretroviral Treatment Does Not Normalize the Serum Level of Soluble CD14

Méndez-Lagares, Gema; Romero-Sánchez, M. Concepción; Ruiz‐Mateos, Ezequiel; Genebat, Miguel; Ferrando‐Martínez, Sara; Muñoz‐Fernández, María Ángeles; Pacheco, Yolanda M.; Leal, Manuel

doi:10.1093/infdis/jit025

Cited by 73 publications

(59 citation statements)

References 15 publications

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“…In the current study, median sCD163, sCD14, and IL-2sRα values were significantly higher in the HIV-infected than uninfected group, in keeping with prior data[24, 28, 29, 84]. sCD163 independently associated with worse pulmonary dysfunction, including lower FEV 1 /FVC post-bronchodilator ratio, greater odds of bronchodilator responsiveness, and lower DL CO percent-predicted in HIV-infected participants.…”

Section: Discussionsupporting

confidence: 90%

“…Commonly measured markers of monocyte activation include sCD163, a circulating molecule which is enzymatically cleaved from monocytes upon activation[74], and sCD14. Both markers are elevated in HIV infection, including among persons with viral control[24, 25, 27, 28]. Additionally, both are increased in inflammatory HIV-associated non-AIDS conditions such as cardiovascular disease, atherosclerosis,[20, 29, 75–78] and HIV-associated neurocognitive disorders[22, 23, 26, 79].…”

Section: Discussionmentioning

confidence: 99%

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Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Fitzpatrick

Nouraie

Gingo

et al. 2016

Aids

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Objective Chronic obstructive pulmonary disease (COPD) is a common co-morbidity in HIV, with prevalence and severity of disease incompletely explained by risk factors such as smoking and age. Unique HIV-associated factors, including microbial translocation, monocyte activation, and endothelial dysfunction, have been described in other co-morbidities, but have not been investigated in relation to pulmonary abnormalities in HIV. This study assessed the relationship of these pathologic processes to pulmonary function in HIV-infected and uninfected individuals and determined if relationships were unique to HIV. Design Longitudinal observational study Methods 274 participants completed pulmonary function testing. Markers of inflammation (IL-6, IL-8, TNF-α), microbial translocation (lipopolysaccharide, sCD14), monocyte activation (sCD163, sCD14, and IL-2 receptor), and endothelial dysfunction (endothelin-1) were measured at baseline. Cross-sectional and longitudinal analyses were performed, adjusting for pertinent covariates. Results In HIV-infected individuals, higher IL-6 and endothelin-1 associated with worse FEV1 percent-predicted, and higher sCD163 associated with worse FEV1/FVC. IL-6, TNF-α, lipopolysaccharide, sCD163, IL-2 receptor, and endothelin-1 associated with diffusing impairment. sCD163 and endothelin-1 interacted with HIV status in relationship to pulmonary function. In HIV-infected individuals only, baseline endothelin-1 was associated with lower FEV1, and sCD163 and endothelin-1 were associated with lower diffusing capacity during follow-up. Conclusions Circulating markers of HIV-associated humoral abnormalities are associated with airflow obstruction and diffusing impairment, and baseline measures of monocyte activation and endothelial dysfunction associate with lower pulmonary function over time in HIV-infected persons. These findings suggest mechanisms of the disproportionate burden of COPD in HIV-infected persons.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Fitzpatrick

Nouraie

Gingo

et al. 2016

Aids

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“…However, it is also possible that the increased IDO activity was induced by microbial products that translocated from the leaky gut in HIV-infected patients, as many microbes and microbial components were shown to be capable of inducing IDO [31]–[34]. In agreement with previous studies, the plasma sCD14 levels did not change significantly despite 1 year of effective antiretroviral therapy in our study, suggesting that HAART may not restore the intestinal barrier function, resulting in persistent microbial translocation and immune activation [25], [27], [35], [36]. Interestingly, IDO activity was also not normalized after 1 year of therapy, indicating that another factor distinct from HIV (e.g.…”

Section: Discussionsupporting

confidence: 90%

Anti-Retroviral Therapy Decreases but Does Not Normalize Indoleamine 2,3-Dioxygenase Activity in HIV-Infected Patients

et al. 2014

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BackgroundIndoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.MethodsWe measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).ResultsAmong 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity.ConclusionsIDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.

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“…After activation, monocytes produce soluble CD14 (sCD14) by enzymatic shedding of CD14 from the plasma membrane [82]. Plasma levels of sCD14 are significantly elevated in HIV-infected persons, regardless of cART treatment status, compared with healthy controls [83, 84]. The plasma level of sCD14 in HIV-infected persons is an independent predictor of mortality and correlates with levels of the inflammatory molecules IL-6, CRP, serum amyloid A, and D-dimer [85].…”

Section: Monocyte Parameters Of Systemic Inflammationmentioning

confidence: 99%

Monocytes as Regulators of Inflammation and HIV-Related Comorbidities during cART

Anzinger

Butterfield

Angelovich

et al. 2014

Journal of Immunology Research

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Combined antiretroviral therapy (cART) extends the lifespan and the quality of life for HIV-infected persons but does not completely eliminate chronic immune activation and inflammation. The low level of chronic immune activation persisting during cART-treated HIV infection is associated with the development of diseases which usually occur in the elderly. Although T-cell activation has been extensively examined in the context of cART-treated HIV infection, monocyte activation is only beginning to be recognized as an important source of inflammation in this context. Here we examine markers and sources of monocyte activation during cART-treated HIV infection and discuss the role of monocytes during cardiovascular disease, HIV-associated neurocognitive disorder, and innate immune aging.

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Long-Term Suppressive Combined Antiretroviral Treatment Does Not Normalize the Serum Level of Soluble CD14

Cited by 73 publications

References 15 publications

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Novel relationships of markers of monocyte activation and endothelial dysfunction with pulmonary dysfunction in HIV-infected persons

Anti-Retroviral Therapy Decreases but Does Not Normalize Indoleamine 2,3-Dioxygenase Activity in HIV-Infected Patients

Monocytes as Regulators of Inflammation and HIV-Related Comorbidities during cART

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