Implication of Interleukin (IL)-18 in the pathogenesis of chronic obstructive pulmonary disease (COPD).
Interleukin (IL)-18 is a pro-inflammatory cytokine that was firstly described as an interferon (IFN)-γ-inducing factor. Similar to IL-1β, IL-18 is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine. The platform for activating caspase-1 is known as the inflammasome, a multiple protein complex. Macrophages and dendritic cells are the primary sources for the release of active IL-18, whereas the inactive precursor remains in the intracellular compartment of mesenchymal cells. Finally, the IL-18 precursor is released from dying cells and processed extracellularly. IL-18 has crucial host defense and antitumor activities, and gene therapy to increase IL-18 levels in tissues protects experimental animals from infection and tumor growth and metastasis. Moreover, multiple studies in experimental animal models have shown that IL-18 over-expression results to emphysematous lesions in mice. The published data prompt to the hypothesis that IL-18 induces a broad spectrum of COPD-like inflammatory and remodeling responses in the murine lung and also induces a mixed type 1, type 2, and type 17 cytokine responses. The majority of studies identify IL-18 as a potential target for future COPD therapeutics to limit both the destructive and remodeling processes occurring in COPD lungs.
1st Department of Respiratory Medicine, Medical School, National and Kapodistrian University of Athens and "Sotiria" Chest Disease Hospital, 11527 Athens, Greece.
Efrossini
E
Dima
1st Department of Respiratory Medicine, Medical School, National and Kapodistrian University of Athens and "Sotiria" Chest Disease Hospital, 11527 Athens, Greece.
Ourania
O
Koltsida
Pumonary Department, Intensive Care Medicine, Evaggelismos Hospital, Medical School, University of Athens, Greece.
Paraskevi
P
Katsaounou
1st Department of Respiratory Medicine, Medical School, National and Kapodistrian University of Athens and "Sotiria" Chest Disease Hospital, 11527 Athens, Greece.
Sofia
S
Vakali
1st Department of Respiratory Medicine, Medical School, National and Kapodistrian University of Athens and "Sotiria" Chest Disease Hospital, 11527 Athens, Greece.
Antonia
A
Koutsoukou
1st Department of Respiratory Medicine, Medical School, National and Kapodistrian University of Athens and "Sotiria" Chest Disease Hospital, 11527 Athens, Greece.
Nikolaos G
NG
Koulouris
1st Department of Respiratory Medicine, Medical School, National and Kapodistrian University of Athens and "Sotiria" Chest Disease Hospital, 11527 Athens, Greece. Electronic address: nikrovina@med.uoa.gr.
Nikoletta
N
Rovina
D000818:Animals; D020170:Caspase 1 / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D020382:Interleukin-18 / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D051379:Mice; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology
C000589760:IL18 protein, human; D020382:Interleukin-18; D020170:Caspase 1
Chronic obstructive pulmonary disease; Inflammasome; Interleukin (IL)-18