title: Low interleukin (IL)-18 levels in sputum supernatants of patients with severe refractory asthma.
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.
authors.affiliation: 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.
authors.forename: Nikoletta
authors.initials: N
authors.lastname: Rovina
authors.affiliation: National and Kapodistrian University of Athens, 1st Department of Pulmonary Medicine, "Sotiria" District Chest Diseases Hospital, Athens Medical School, Greece.
authors.forename: Efrossini
authors.initials: E
authors.lastname: Dima
authors.affiliation: National and Kapodistrian University of Athens, 1st Department of Pulmonary Medicine, "Sotiria" District Chest Diseases Hospital, Athens Medical School, Greece.
authors.forename: Petros
authors.initials: P
authors.lastname: Bakakos
authors.affiliation: National and Kapodistrian University of Athens, 1st Department of Pulmonary Medicine, "Sotiria" District Chest Diseases Hospital, Athens Medical School, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Tseliou
authors.affiliation: National and Kapodistrian University of Athens, 1st Department of Pulmonary Medicine, "Sotiria" District Chest Diseases Hospital, Athens Medical School, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Kontogianni
authors.affiliation: National and Kapodistrian University of Athens, 2nd Department of Pulmonary Medicine, "Atticon" Hospital, Athens Medical School, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Papiris
authors.affiliation: National and Kapodistrian University of Athens, 1st Department of Pulmonary Medicine, "Sotiria" District Chest Diseases Hospital, Athens Medical School, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Koutsoukou
authors.affiliation: National and Kapodistrian University of Athens, 1st Department of Pulmonary Medicine, "Sotiria" District Chest Diseases Hospital, Athens Medical School, Greece.
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Koulouris
authors.affiliation: National and Kapodistrian University of Athens, 2nd Department of Pulmonary Medicine, "Atticon" Hospital, Athens Medical School, Greece.
authors.forename: Stelios
authors.initials: S
authors.lastname: Loukides
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D004804:Eosinophils / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020382:Interleukin-18 / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012129:Respiratory Function Tests / Q000379:methods; D012882:Skin Tests; D012907:Smoking / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013183:Sputum / Q000737:chemistry / Q000378:metabolism* / Q000382:microbiology
chemical_list: D020382:Interleukin-18
keywords: Airway viral and bacterial colonization; IL-18; Inflammation; Severe refractory asthma