Independent Associations of Tumor Necrosis Factor-Alpha and Interleukin-1 Beta With Radiographic Emphysema in People Living With HIV

Abstract

BackgroundPeople living with HIV (PLWH) have increased systemic inflammation, and inflammation has been suggested to contribute to the pathogenesis of emphysema. We investigated whether elevated cytokine concentrations (interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), soluble CD14 (sCD14) and sCD163 were independently associated with radiographic emphysema in PLWH.MethodsWe included PLWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study without hepatitis B and C co-infection and with a plasma sample and a chest computed tomography scan available. Emphysema plus trace emphysema was defined as the percentage of low attenuation area under −950 Houndsfield Unit (%LAA-950) using a cut-off at 5%. Cytokine concentrations were measured by ELISA or Luminex immunoassays. An elevated cytokine concentration was defined as above the 75th percentile.ResultsOf 783 PLWH, 147 (18.8%) had emphysema. PLWH were predominantly male (86.0%) and 743 (94.9%) had undetectable viral replication. PLWH with emphysema had higher concentrations of TNFα (median (IQR): 8.2 (6.4-9.8) versus 7.1 (5.7-8.6) pg/ml, p<0.001), IL-1β (0.21 (0.1-0.4) versus 0.17 (0.1-0.3) pg/ml, p=0.004) and IL-6 (3.6 (2.6-4.9) versus 3.1 (2.0-4.3) pg/ml, p=0.023) than PLWH without. In a logistic regression model adjusted for age, sex, ethnicity, smoking status, BMI and CD4 nadir, elevated TNFα (adjusted odds ratio (aOR): 1.78 [95%CI: 1.14-2.76], p=0.011) and IL-1β (aOR: 1.81 [95%CI: 1.16-2.81], p=0.009) were independently associated with emphysema. The association between IL-1β and emphysema was modified by smoking (p-interaction=0.020) with a more pronounced association in never-smokers (aOR: 4.53 [95%CI: 2.05-9.98], p<0.001).ConclusionTwo markers of systemic inflammation, TNFα and IL-1β, were independently associated with emphysema in PLWH and may contribute to the pathogenesis of emphysema. Importantly, the effect of IL-1β seems to be mediated through pathways that are independent of excessive smoking.Clinical Trial Registrationclinicaltrials.gov, identifier NCT02382822.

Gut Microbiota Alterations and Circulating Imidazole Propionate Levels Are Associated With Obstructive Coronary Artery Disease in People With HIV

“…Plasma samples were collected and stored at −80°C until use. Interleukin 6 (IL-6) was measured by enzyme immunoassays and ImP by liquid chromatography-tandem mass spectrometry, as previously described ( https://bevital.no ) [ 14 , 19 ].…”

Clonal hematopoiesis of indeterminate potential in persons with HIV

“…For analyses of inflammatory markers, plasma samples were collected at baseline and stored at À80 8C until use. The methods used for analyses of IL-1b, IL-1Ra, IL-2, IL-6, IL-10, soluble CD14, soluble CD163 and TNF-a have been described in detail elsewhere [18,21,22]. All analyses were done according to the manufacturer's instructions.…”

COPD in People with HIV: Epidemiology, Pathogenesis, Management, and Prevention Strategies

“… 190 In addition, Leung et al found that people with low DLco and a combination of centrilobular and paraseptal emphysema were more likely to have progression of emphysema, 191 and significant emphysema burden was associated with increased mortality. 192 Elevated TNFα and IL-1β, soluble CD14, nadir CD4, and low CD4/CD8 ratio are also independently associated with emphysema in PWH, 140 , 193 , 194 although reports of a direct association of HIV with emphysema are contradictory. 194 , 195 While the exact mechanisms are an area of active investigation, HIV-mediated chronic inflammation and immune dysregulation likely play an important role in emphysema formation.…”