Smoking and Interleukin-1 Activity Released from Human Alveolar Macrophages in Healthy Subjects

doi:10.1378/chest.94.4.694

Chest

Volume 94, Issue 4, October 1988, Pages 694-700

https://doi.org/10.1378/chest.94.4.694 Get rights and content

To evaluate the activation of alveolar macrophages from smoking, we studied interleukin-1 (IL-1) activity released from alveolar macrophages in eight healthy smokers, compared to 12 healthy nonsmokers. We used 24-hour culture supernatants containing IL-1 of bronchoalveolar lavage fluid (BALF) macrophages/blood monocytes with or without LPS stimulation. Using C3H/HeJ thymocyte PHA costimulation assay, we found that IL-1 activity released from LPS stimulated BALF macrophages was significantly higher in smokers (2.39 ± 0.33 U/ml) than in nonsmokers (1.47 ± 0.19 U/ml, p<0.05). We also detected IL-1 inhibitory activity in supernatants by using IL-1 inhibitory assay. The inhibitory activity was higher in nonsmokers than in smokers especially under LPS stimulation. The presence of inhibitory (actors other than prostaglandin-E₂, was suggested from the differential response to the addition of indomethacin into cultures from nonstimulated and LPS-stimulated supernatants of BALF macrophages. (Chest 1988; 94:694-700)

Section snippets

Study Population

We studied 20 healthy volunteers; 12 were nonsmokers and eight smokers. The smokers smoked 24.4 ± 3.4 of cigarette per day, with Brinkman index of 333 ± 124 pack years (mean ± SE). None of the subjects had any signs and symptoms of infection or inflammation. X-ray films, pulmonary function, and routine laboratory test results were normal.

Preparation of BALF and Blood Mononuclear Cells

The BAL was performed as previously described with slight modification.⁵ Briefly, the upper airways were anesthetized with 4 percent xylocaine. The fiberoptic

BALF Cell Findings

In smokers, there was a significant (p<0.05) increase in recovered cells per milliliter and macrophages (percent). The lymphocyte count and CD4⁺/CD8⁺ ratio were significantly (p<0.05) reduced in smokers as compared to nonsmokers. The percentages of neutrophils and eosinophil were similar in both groups (Table 1).

IL-1 Activity Released from BALF Macrophages and Blood Monocytes

Spontaneously released IL-1 activity was much lower in BALF macrophages than in blood monocytes. When BALF macrophages and blood monocytes were stimulated with LPS, the IL-1 activity

DISCUSSION

The role of IL-1 in the inflammatory process in the lung has been widely discussed.8, 9, 10 Some have referred to the influence of smoking on the inflammatory process and lung injury in pulmonary emphysema and fibrotic lung diseases.²

Lavage cell populations from healthy smokers display characteristic changes.11, 12 Smokers' BALF contains an increased number of alveolar macrophages which are also morphologically different from the nonsmokers'.⁴ The BALF macrophage in healthy smokers is about

ACKNOWLEDGMENT

Our thanks are due to M. Emura, M.D., T. Mio, M.D., M. Kitaichi, M.D., and residents who so kindly performed bronchoalveolar lavages; Mrs. F. Tanioka who provided valuable technical help to our experiments; and Om. P. Sharma, M.D., for review of the manuscript

REFERENCES (28)

U. Costabel et al.
Alterations in immunoregulatory T cell subsets in cigarette smokers: a phenotypic analysis of bronchoalveolar and blood lymphocytes
Chest
(1986)
D.E. Niewoehner et al.
Cigarette smoking and the development of chronic airflow limitation
Curr Pulmonol
(1986)
J. Chretien et al.
Tobacco smoke and alveolar cell populations
J.J. Oppenheim et al.
There is more than one interleukin-1
Immunol Today
(1986)
S. Nagai et al.
Differentiation between idiopathic pulmonary fibrosis and interstitial pneumonia associated with collagen vascular disease by comparison of the ratio of OKT4⁺ cells and OKT8⁺ cells in BALF T lymphocytes
Eur J Respir Dis
(1985)
T. Izumi et al.
Clinical value of the measurement of bronchoalveolar lavage fluid cell subsets in interstitial lung diseases
Chest
(1986)
S.B. Mizel
Production and quantitation of lymphocyte activating factor (interleukin-1)
G.W. Hunninghake
Release of IL-1 by alveolar macrophages of patients with active pulmonary sarcoidosis
Am Rev Respir Dis
(1984)
M.K. Kleinhenz et al.
Interleukin-1 production by blood monocytes and bronchoalveolar cells in sarcoidosis
Ann NY Acad Sci
(1986)
S. Nagai et al.
The significance of IL-1 and the IL-1 inhibitory factor in the evaluation of inflammatory state in sarcoidosis and idiopathic pulmonary fibrosis
Am Rev Respir Dis
(1987)

G.W. Hunninghake et al.

Inflammatory and immune process in the human lung in health and disease: evaluation by bronchoalveolar lavage

Am J Pathol

(1979)

P.G. Holt

Immune and inflammatory function in cigarette smokers

Thorax

(1987)

D.O. Adams et al.

The cell biology of macrophage activation

Ann Rev Immunol

(1984)

N. Clerici et al.

Expression of Ia like (HLA-DR) antigens on human alveolar macrophages

Clin Exp Immunol

(1984)

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Thus, the GM-MØ system was further utilized to determine whether the reduction of individual class I HDACs – HDAC3 in the case of smokers or HDAC2 in the case of COPD patients – would affect the inflammatory phenotype of GM-MØ in the absence of cigarette smoke. IL1β and IL8 were selected as the read-outs for these studies because their expression is increased in the BALF and sputum of smokers [18–26], their production is increased in ex vivo cultures of smokers' AM [12,27–31], and their mRNA expression was significantly increased by cigarette smoke in the GeneChip study detailed above (data not shown). Commercially available pools of siRNA targeting HDACs 1, 2, or 3 were used to specifically target these individual class I HDAC isoforms in GM-MØ derived from 11 monocyte donors.
Chronic obstructive pulmonary disease (COPD) is a debilitating condition resulting from exposure to pollutants such as cigarette smoke. Pulmonary macrophages secrete a plethora of inflammatory mediators that are increased in the lungs of COPD patients, but whether this phenotype results directly from smoke exposure remains unknown. Using an in vitro model for alveolar macrophages (AM) derived from human peripheral blood monocytes with granulocyte-macrophage stimulating factor (GM-MØ), we analyzed the mechanistic connection between cigarette smoke exposure and histone deacetylase (HDAC) regulation, hypothesized to be a contributing factor in COPD pathophysiology. Here we show that acute smoke exposure inhibits HDAC enzymatic activity in GM-MØ. Analysis of mRNA and total cellular proteins for expression of class I (1, 2, 3 and 8), class II (4, 5, 6, 7, 9, 10), and class IV (11) HDAC revealed no effect of smoke exposure, whereas nuclear HDAC3 protein content was reduced. To better understand the physiological significance of reduced HDAC3 activity, we utilized siRNA to knockdown HDAC1, 2 and 3 individually. Interestingly, siRNA-mediated reduction of HDAC3 resulted in increased production of IL8 and IL1β in response to LPS stimulation, while HDAC2 knockdown had no effect on either cytokine. Lower nuclear content of HDAC3 in the context of equivalent total HDAC protein levels following smoke exposure may reflect increased nuclear export of HDAC3, allowing increased nuclear factor kappa b (NF-κB ) driven cytokine expression that can contribute to inflammation.
Interaction between interleukin-1β -31T/C gene polymorphism and drinking and smoking habits on the risk of hepatocellular carcinoma among Japanese
2008, Cancer Letters
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There is evidence showing that moderate alcohol intake in humans reduces the production of IL-1β and TNF-α through inhibition of NF-κB [20] and that in vitro exposure of cultured cells to ethanol in high concentrations reduced the IL-1β and TNF-α induced cytokine generation by inhibiting translocation of NF-κB subunits to the nucleus [27]. Smoking has been shown to increase the production of IL-1β and TNF-α by macrophages [21,28]. These properties might contribute to the potential risk modification for the IL-1B −31T/C genotype by alcohol and tobacco although the precise mechanisms remain to be elucidated.
The risk of hepatocellular carcinoma (HCC) increases with the severity of hepatic inflammation. Interleukin (IL)-1β and tumor necrosis factor (TNF)-α are proinflammatory cytokines with multiple biological effects and may play essential roles in inflammation-linked tumor development. We conducted a case-control study including 209 incident HCC cases and two control groups (275 hospital controls and 381 patients with chronic liver disease [CLD] without HCC) to investigate whether IL-1B and TNF-A gene polymorphisms influence HCC susceptibility with any interaction with alcohol and tobacco. By comparing HCC cases with CLD patients, we found that IL-1B −31T/C polymorphism was associated with HCC risk among never drinkers and current smokers; adjusted odds ratios (and 95% confidence intervals) for C/T and T/T genotypes compared with C/C genotype were 1.70 (0.76–3.77) and 2.46 (1.05–5.76) (P trend = 0.03), respectively, among never drinkers, and 1.53 (0.60–3.99) and 2.54 (0.81–7.95) (P trend = 0.11), respectively, among current smokers. Similarly, HCC risk associated with heavy alcohol intake and current smoking differed by this polymorphism among CLD patients. IL-1B −31T/C polymorphism may modify HCC risk in relation to alcohol intake or smoking.
Influence of smoking on the expression of various cytokines in murine bronchoalveolar lavage fluid cells
1996, Allergology International
The cytokine network plays an important role in the pathogenesis of allergic asthmatic lung. As the influence of smoking on cytokine expression should be considered in delineating the cytokine network, the effects of a single exposure and chronic exposure to smoke on the number and cytokine expression of bronchoalveolar lavage fluid (BALF) cells were evaluated. From a total of 126 BALB/c mice, BALF cells were obtained and analyzed using the quantitative reverse transcription-polymerase chain reaction technique (RT-PCR).
The bodyweights of chronic smoking mice were found to be lower when compared to those mice that had not been exposed to smoke. The total number of BALF cells increased after smoking without significant differences in cell classification. Spontaneous mRNA expression of interleukin-1α (IL-1α), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-1β) was detected in all cases. The time courses of their expression patterns after exposure to smoke were similar between the chronic and single smoking mice, except for TGF-β. The levels of IL-1β, IL-1β and TGF-β mRNA increased immediately after the exposure to smoke in chronic smoking mice, whereas the levels of TGF-β mRNA increased 2 h after exposure in the single smoking mice. Moreover, the increase of IL-1α and TGF-1β mRNA in the early phase after exposure was exaggerated in chronic smoking mice.
Thus, repeated exposure to smoke may have caused some alterations in the expression mechanism of cytokines such as TGF-β and IL-1α in BALF cells, while it seemed to cause a repeated pattern of acute inflammation after each exposure. In the evaluation of cytokine expression in BALF cells in smokers with various lung diseases, it is recommended that before taking samples a sufficient time interval after the last exposure to smoke be allowed to avoid the effect of acute inflammation caused by smoking.
Relative release of interleukin-1β and interleukin-1 receptor antagonist by alveolar macrophages: A study in asbestos-induced lung disease, sarcoidosis, and idiopathic pulmonary fibrosis
1993, Chest
We examined the influence of untreated interstitial lung disease (ILD) on the in vitro release of interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1ra) from alveolar macrophages (AM); AM were harvested from normal volunteers, ILD patients, and patients with asbestos-related pleural disease but no ILD. AM were cultured for 24 h and assays for IL-1β and IL-1ra were done using sensitive and specific enzyme-linked immunosorbent assay. A greater amount of IL-1β was detected in AM supernatants from asbestosis, sarcoidosis, and IPF patients than in those from normal subjects. The IL-1β: IL-1ra ratio (IL-1β activity index [IL-1AI]) was significantly lower in supernatants of normal macrophages compared with macrophage supernatants from individuals with ILD. The IL-1AI correlated with bronchoalveolar lavage cellularity, a marker of disease activity. Current smoking was associated with lower IL-1β and IL-1ra release in ILD. The IL-1AI is a convenient method for comparison of IL-1β activity between patient populations.
IL-1 and IL-1 inhibitory activity in the culture supernatants of alveolar macrophages from patients with interstitial lung diseases
1991, Chest
Under normal conditions, the release of interleukin 1 (IL-1) and IL-1 inhibitors play a role in tissue homeostasis. We have already reported an increase in IL-1 activity and a decrease in IL-1 inhibitory activity (IHA) in the supernatants of alveolar macrophages from healthy long-term smokers as compared with healthy nonsmokers. In this study, we report an alteration in the release of IL-1 and IL-1 IHA from alveolar macrophages in patients with interstitial lung diseases (sarcoidosis and idiopathic pulmonary fibrosis [IPF]). IL-1 activity released from alveolar macrophages stimulated by lipopolysaccharide was increased in patients with active sarcoidosis (mean ± SD, 2.52 ± 1.33 U/ml [n = 6] vs 1.38 ± 0.62 U/ml [n = 15] for healthy noncurrent smokers [HNS]; p<0.05). IL-1 IHA released from alveolar macrophages was significantly different among the groups examined: a decrease of IL-1 IHA occurred in patients with active sarcoidosis (61.4 ± 19.2 [n = 6] vs 85.9 ± 13.9 percent: HNS; p<0.05) and IPF (64.7 ± 18.5 [n = 9]; p<0.05). Prednisolone in the culture medium at physiologic concentrations suppressed the release of IL-1 and enhanced the release of IL-1 IHA. IL-1 IHA inhibited not only mouse thymocyte proliferation but also human fibroblast proliferation in the presence of EL-1. (Chest 1991; 99:674–80)
Cigarette smoke exposure inhibits early phase of antibody production through inhibition of immune functions in alveolar macrophage
2020, Current Respiratory Medicine Reviews

View all citing articles on Scopus

This study was supported by grants from the Smoking Research Foundation in Japan.

Manuscript received December 28; revision accepted March 28

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Chest

Smoking and Interleukin-1 Activity Released from Human Alveolar Macrophages in Healthy Subjects

Section snippets

Study Population

Preparation of BALF and Blood Mononuclear Cells

BALF Cell Findings

IL-1 Activity Released from BALF Macrophages and Blood Monocytes

DISCUSSION

ACKNOWLEDGMENT

Chest

Cigarette smoking and the development of chronic airflow limitation

Curr Pulmonol

Tobacco smoke and alveolar cell populations

There is more than one interleukin-1

Immunol Today

Differentiation between idiopathic pulmonary fibrosis and interstitial pneumonia associated with collagen vascular disease by comparison of the ratio of OKT4+ cells and OKT8+ cells in BALF T lymphocytes

Eur J Respir Dis

Clinical value of the measurement of bronchoalveolar lavage fluid cell subsets in interstitial lung diseases

Chest

Production and quantitation of lymphocyte activating factor (interleukin-1)

Release of IL-1 by alveolar macrophages of patients with active pulmonary sarcoidosis

Am Rev Respir Dis

Interleukin-1 production by blood monocytes and bronchoalveolar cells in sarcoidosis

Ann NY Acad Sci

The significance of IL-1 and the IL-1 inhibitory factor in the evaluation of inflammatory state in sarcoidosis and idiopathic pulmonary fibrosis

Am Rev Respir Dis

Inflammatory and immune process in the human lung in health and disease: evaluation by bronchoalveolar lavage

Am J Pathol

Immune and inflammatory function in cigarette smokers

Thorax

The cell biology of macrophage activation

Ann Rev Immunol

Expression of Ia like (HLA-DR) antigens on human alveolar macrophages

Clin Exp Immunol

Differentiation between idiopathic pulmonary fibrosis and interstitial pneumonia associated with collagen vascular disease by comparison of the ratio of OKT4⁺ cells and OKT8⁺ cells in BALF T lymphocytes