Low interleukin (IL)-18 levels in sputum supernatants of patients with severe refractory asthma

Nikoletta Rovina; Efrossini Dima; Petros Bakakos; Eleni Tseliou; Konstantina Kontogianni; Spyros Papiris; Antonia Koutsoukou; Nikolaos G Koulouris; Stelios Loukides

doi:10.1016/j.rmed.2015.03.002

Low interleukin (IL)-18 levels in sputum supernatants of patients with severe refractory asthma

Respir Med. 2015 May;109(5):580-7. doi: 10.1016/j.rmed.2015.03.002. Epub 2015 Mar 19.

Authors

Nikoletta Rovina¹, Efrossini Dima², Petros Bakakos², Eleni Tseliou², Konstantina Kontogianni², Spyros Papiris³, Antonia Koutsoukou², Nikolaos G Koulouris², Stelios Loukides³

Affiliations

¹ National and Kapodistrian University of Athens, 1st Department of Pulmonary Medicine, "Sotiria" District Chest Diseases Hospital, Athens Medical School, Greece. Electronic address: nikrovina@med.uoa.gr.
² National and Kapodistrian University of Athens, 1st Department of Pulmonary Medicine, "Sotiria" District Chest Diseases Hospital, Athens Medical School, Greece.
³ National and Kapodistrian University of Athens, 2nd Department of Pulmonary Medicine, "Atticon" Hospital, Athens Medical School, Greece.

PMID: 25840484
DOI: 10.1016/j.rmed.2015.03.002

Abstract

Background: Severe refractory asthma (SRA) is characterized by persistent asthma symptoms, amplified airway inflammation despite treatment with high dose inhaled steroids and increased airway bacterial colonization. Interleukin (IL)-18 is a pleiotropic pro-inflammatory cytokine that modulates airway inflammation. Furthermore, as a product of the inflammasome, IL-18 is involved in host defence against viral and bacterial stimuli by modulating the immune response.

Objective: To determine IL-18 levels in sputum supernatants of patients with asthma and to investigate whether underlying severity affects its levels. Furthermore, possible associations with atopy and mediators and cells involved in the inflammatory process of the airways were examined.

Methods: Forty-five patients with mild intermittent asthma (21 smokers) and 18 patients with SRA in stable state were studied. All subjects underwent lung function tests, skin prick tests, and sputum induction for cell count identification. IL-18 and ECP levels were measured in sputum supernatants. Furthermore, sputum samples were examined for the commonest respiratory pathogens and viruses by real time polymerase chain reaction (RT-PCR).

Results: Patients with SRA had significantly lower IL-18 levels in sputum supernatants compared to mild asthmatics (p < 0.001). Twelve out of eighteen patients with SRA were colonized by viruses and/or bacterial pathogens. IL-18 levels correlated with the percentage of macrophages (r = 0.635, p = 0.026) and inversely correlated with the percentage of neutrophils in sputum (r = -0.715, p = 0.009). No correlations were found between IL-18, ECP and the percentage of eosinophils in the sputum of SRA.

Conclusions: In SRA IL-18 is possibly involved in chronic airway inflammation through an eosinophil independent pathway. The decreased levels of IL-18 in SRA support the hypothesis of deregulated inflammasome activation, justifying the susceptibility of these patients for bacterial colonization or infection.

Keywords: Airway viral and bacterial colonization; IL-18; Inflammation; Severe refractory asthma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Airway Remodeling
Asthma / immunology
Asthma / metabolism*
Asthma / pathology
Cohort Studies
Eosinophils / metabolism
Eosinophils / pathology
Female
Humans
Inflammation / immunology
Inflammation / metabolism
Inflammation / pathology
Interleukin-18 / analysis
Interleukin-18 / metabolism*
Male
Middle Aged
Neutrophils / metabolism
Neutrophils / pathology
Real-Time Polymerase Chain Reaction
Respiratory Function Tests / methods
Skin Tests
Smoking / immunology
Smoking / metabolism
Smoking / pathology
Sputum / chemistry
Sputum / metabolism*
Sputum / microbiology

Substances

Interleukin-18