Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes.
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-2Ralpha) 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-2Ralpha 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.
Andersson
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Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden. Anders.Andersson@lungall.gu.se
Qvarfordt
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Laan
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Sjostrand
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Malmhall
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Riise
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Cardell
L-O
LO
Linden
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D000328:Adult; D000368:Aged; D001991:Bronchitis / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019410:Interleukin-16 / Q000032:analysis*; D053645:Interleukin-2 Receptor alpha Subunit; D008221:Lymphoid Tissue / Q000737:chemistry* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000737:chemistry / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000032:analysis; D012906:Smoke / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000737:chemistry* / Q000276:immunology
C508017:IL2RA protein, human; D019410:Interleukin-16; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D012906:Smoke