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.
Highlights
During the current combination antiretroviral therapy era, comorbidities such as chronic pulmonary diseases are more prevalent in people living with human immunodeficiency virus (HIV) (PLWH) than in the background population [1,2,3]
We investigated whether elevated cytokine concentrations (interleukin (IL)-1b, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNFa), interferon-gamma (IFNg), soluble CD14 and soluble CD163 (sCD163) were independently associated with radiographic emphysema in people living with HIV (PLWH)
The association between interleukin-1 beta (IL-1b) and emphysema was modified by smoking with a more pronounced association in never-smokers
Summary
During the current combination antiretroviral therapy (cART) era, comorbidities such as chronic pulmonary diseases are more prevalent in people living with HIV (PLWH) than in the background population [1,2,3]. Markers of systemic inflammation, such as the pro-inflammatory cytokine interleukin-6 (IL-6), have been tightly linked to comorbidities and mortality in PLWH [13,14,15]. People 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)-1b, IL-1 receptor antagonist (IL-1RA), IL-2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNFa), interferon-gamma (IFNg), soluble CD14 (sCD14) and sCD163 were independently associated with radiographic emphysema in PLWH
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