IL-18 might reflect disease activity in mild and moderate asthma exacerbation

doi:10.1067/mai.2001.112275

Journal of Allergy and Clinical Immunology

Volume 107, Issue 2, February 2001, Pages 331-336

https://doi.org/10.1067/mai.2001.112275 Get rights and content

Abstract

Background: IL-18, identified as an IFN-γ–inducing factor, is a proinflammatory cytokine that plays an important role in T_H1 cell activation. Recently, it was reported that histamine induced IL-18 and that IL-18 might act as a coinducer of T_H1 and T_H2 cytokines. Objective: The aim was to evaluate the contribution of IL-18 to asthma exacerbation. Methods: Serum IL-18, soluble IL-2 receptor, eosinophil cationic protein, and plasma IFN-γ levels, as well as peak expiratory flow were measured in patients with stable asthma (n = 28), acute mild or moderate asthma (n = 23), or pulmonary sarcoidosis (n = 35) and in healthy subjects (n = 26). We compared the serum IL-18 levels between patients with acute asthma and those in remission and examined the time course in acute exacerbation after asthma therapy. Results: Significantly higher serum IL-18 levels were found in patients with acute asthma (215 ± 33 pg/mL, mean ± SE; P = .02) and pulmonary sarcoidosis (239 ± 27 pg/mL, P = .008) than in control subjects (127 ± 11 pg/mL), but the plasma IFN-γ level was significantly elevated in only pulmonary sarcoidosis (P < .001). In pulmonary sarcoidosis the IL-18 values significantly correlated with the IFN-γ levels (r = 0.61, P < .001), but in acute asthma they did not. The IL-18 levels during acute asthma exacerbation were significantly higher (P = .01) than on remission days. In acute asthma, circulating IL-18 levels significantly correlated with serum soluble IL-2 receptor levels (r = 0.77, P < .0001) but not with serum eosinophil cationic protein levels. The IL-18 level had a tendency to inversely correlate with peak expiratory flow. The elevated IL-18 levels in acute asthma quickly decreased on day 3 (P = .02) and day 7 (P = .002) after therapy. Conclusion: It was suggested that IL-18 may play a potential role to activate immunologic responses and may reflect disease activity in mild and moderate asthma exacerbation. (J Allergy Clin Immunol 2001;107:331-6.)

Section snippets

Study population

All patients and healthy volunteers were recruited from Sapporo Medical University Hospital and Sapporo Hospital of Hokkaido Railway Company, and all gave informed consent. We excluded patients with hepatitis to eliminate its influence.

Asthma

Twenty-eight patients with stable asthma (55 ± 6 years old, 16 women and 12 men), and 23 patients with acute disease (52 ± 7 years old, 15 women and 8 men) were recruited. Asthma was diagnosed with the American Thoracic Society guidelines,¹⁹ according to which 4

Results

IL-18 levels in the sera of patients with stable asthma (155 ± 80 pg/mL), patients with acute asthma (233 ± 33 pg/mL), patients with pulmonary sarcoidosis (239 ± 27 pg/mL), and healthy control subjects (127 ± 11 pg/mL) are shown in Fig 1.

. Serum IL-18 levels in patients with stable and acute asthma, patients with pulmonary sarcoidosis, and healthy control subjects. Dotted line represents the lower limit of the IL-18 assay. Significantly higher values of serum IL-18 were found in patients with

Discussion

We found higher circulating IL-18 levels in patients with acute asthma than in patients with stable asthma and healthy control subjects. The serum IL-18 value had a tendency to correlate inversely with PEF in acute asthma and decreased quickly after asthma therapy. From these results, serum IL-18 values may partly reflect disease activity in mild and moderate asthma. IL-18 is mainly secreted by activated monocytes/macrophages and also by Kupffer cells and other cells.1, 22, 23 IL-18 and IL-12

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^☆: Reprint requests: Hiroshi Tanaka, MD, Third Department of Internal Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, 060-8543, Sapporo, Japan.

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Original Articles: Mechanisms of AllergyIL-18 might reflect disease activity in mild and moderate asthma exacerbation☆

Abstract

Section snippets

Study population

Asthma

Results

Discussion

Adv Immunol

J Allergy Clin Immunol

Am J Pathol

Curr Opin Immunol

Adv Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Cloning of a new cytokine that induces interferon-γ production by T cells

Nature

IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn’s disease: expression and localization in intestinal mucosal cells

J Immunol

A proinflammatory role for IL-18 in rheumatoid arthritis

J Clin Invest

Elevated plasma concentrations of interferon (IFN)-γ and the IFN-γ–inducing cytokines interleukin (IL)-18, IL-12, and IL-15 in severe melioidosis

J Infect Dis

Oversecretion of IL-18 in haemophagocytic lymphohistiocytosis: a novel marker of disease activity

Br J Haematol

Interleukin-18 (IL-18) together with IL-12 inhibits IgE production by induction of IFN-γ production from activated B cells

Proc Natl Acad Sci U S A

IL-18 is a potent coinducer of IL-13 in NK and T cells: a new potential role for IL-18 in modulating the immune response

J Immunol

IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils

Proc Natl Acad Sci U S A

Original Articles: Mechanisms of Allergy
IL-18 might reflect disease activity in mild and moderate asthma exacerbation☆