Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes

Abstract

SUMMARY CD4+ and CD8 + lymphocytes are mobilized in severe chronic obstructive pulmonary disease (COPD) and the CD8 + cytokine interleukin (IL)-16 is believed to be important in regulating the recruitment and activity of CD4 + lymphocytes. In the current study, we examined whether tobacco smoke exerts an impact not only on IL-16 in the lower airways but also in CD4 + or CD8 + lymphocytes or in lymphoid tissue. The concentration of IL-16 protein was measured by enzyme-linked immunosorbent assay (ELISA) in concentrated bronchoalveolar lavage fluid (BALF) collected from 33 smokers with chronic bronchitis (CB), eight asymptomatic smokers (AS) and seven healthy never-smokers (NS). The concentrations of IL-16 and soluble IL-2 receptor alpha (sIL-2R a ) protein were also measured in conditioned medium from human blood CD4+ and CD8 + lymphocytes stimulated with tobacco smoke extract (TSE) in vitro . IL-16 mRNA was assessed in vitro as well, using reverse transcription-polymerase chain reaction (RT-PCR). Finally, the intracellular immunoreactivity for IL-16 protein (IL-16IR) was assessed in six matched pairs of palatine tonsils from smokers and non-smokers. BALF IL-16 was higher in CB and AS than in NS. TSE substantially increased the concentration of IL-16 but not sIL-2R a in conditioned medium from CD4 + and CD8 + lymphocytes. There was no corresponding effect on IL-16 mRNA. IL-16IR in tonsils was lower in smokers than in non-smokers. The current findings demonstrate that tobacco smoke exerts a wide impact on the CD8 + cytokine IL-16, in the airway lumen, in blood CD4 + and CD8 + lymphocytes and in lymphoid tissue. The effect on IL-16 release may be selective for preformed IL-16 in CD4 + lymphocytes. New clinical studies are required to evaluate whether tobacco smoke mobilizes T lymphocytes via IL-16 in the lower airways and whether this mechanism can be targeted in COPD.

Correlates of CD4+ and CD8+ Lymphocyte Counts in High-Risk Immunodeficiency Virus (HIV)-Seronegative Women enrolled in the Women’s Interagency HIV Study (WIHS)

“…Many of these effects of smoking may result from the ability of nicotine to suppress immune system function [18,19]. Thus, nicotine has been reported to increase IL-16 levels, which may influence systemic immunomodulation by altering the number and responsiveness of systemic T lymphocytes in humans [20,21]. Nicotine has also been reported to differentially effect mouse splenocyte proliferation, with production of Th1 versus Th2 cytokines [22,23].…”

Integrative Omics Approach Identifies Interleukin-16 as a Biomarker of Emphysema

“…Two small studies of chronic bronchitis and COPD suggest a possible relationship between IL-16 and COPD. In a study of 33 smokers, BALF IL-16 was reported to be elevated with chronic bronchitis (Andersson et al, 2004) and in a study of 152 COPD patients and 80 controls, plasma IL-16 was lower in males with COPD, but there was no adjustment for potential confounding factors other than gender (de Torres et al, 2011). This study did not investigate emphysema and we are unaware of any studies investigating differences of IL16 mRNA in peripheral blood gene expression.…”

Lung Tissue and Tumour‐infiltrating T Lymphocytes in Patients with Non‐small Cell Lung Carcinoma and Chronic Obstructive Pulmonary Disease (COPD): Moderate/Severe Versus Mild Stage of COPD1

“…Previous researchers showed more CD8 + and CD4 + T cells in the lungs of patients with COPD, chronic bronchitis and even asymptomatic smokers compared with non‐smoking controls [4–15]. Comparing smokers with and without COPD, Saetta et al.…”

“…Lung inflammation is present in all smokers and is comprised of neutrophils, macrophages and T lymphocytes [4–6, 8, 9]. Concerning specific inflammation, CD4 + helper and especially CD8 + cytotoxic T lymphocytes have been shown to be increased in airways and lung parenchyma in COPD patients [4–16]. The excessive recruitment of T cells in the lung could be a consequence of a response to neoantigens induced by cigarette smoke in the case of ‘autoantigenic hypothesis of COPD’ or simply a response to viral infections (active or latent) that are common in this disease [9, 17, 18].…”