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

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.