Enhanced expression of interleukin-18 and its receptor in idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is a major interstitial lung disease (ILD). Recently, we established a new mouse model for ILD in which daily administration of interleukin (IL)-18 with IL-2 induces lethal lung injury, suggesting that IL-18 is involved in the pathogenesis of ILD. Here, utilizing immunohistochemistry, we have analyzed IL-18 and IL-18 receptor (IL-18R) alpha expression in the lungs of 18 patients with IPF/UIP and 13 control subjects by using monoclonal anti-IL-18 antibodies and a new monoclonal antibody for IL-18Ralpha (H44). IL-18 was expressed in bronchoalveolar epithelium, alveolar macrophages, and the endothelium of small vessels in control subjects, and was abundantly expressed in the majority of pulmonary cells in patients with IPF. IL-18Ralpha was expressed in bronchoalveolar epithelium and alveolar macrophages in control subjects, and was strongly expressed in interstitial cells in patients with IPF, especially in the fibroblastic foci (FF). Interestingly, IL-18Ralpha expression was only weakly observed in areas showing established fibrosis. Semiquantitative analysis revealed that the histologic FF score was significantly correlated with the IL-18Ralpha expression level in FF lesions. Moreover, IL-18 levels in the serum and bronchoalveolar lavage fluid of patients with IPF were significantly higher than those in control subjects. Our findings suggest IL-18 and IL-18R are involved in the pathogenesis of IPF/UIP.
Kitasato
Yasuhiko
Y
Department of Internal Medicine 1, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Hoshino
Tomoaki
T
Okamoto
Masaki
M
Kato
Seiya
S
Koda
Yoshiro
Y
Nagata
Nobuhiko
N
Kinoshita
Masaharu
M
Koga
Hideyuki
H
Yoon
Do-Young
DY
Asao
Hironobu
H
Ohmoto
Hiroshi
H
Koga
Takeharu
T
Rikimaru
Toru
T
Aizawa
Hisamichi
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000097:blood / Q000378:metabolism*; D053727:Interleukin-18 Receptor alpha Subunit; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism*; D053724:Receptors, Interleukin-18
D000911:Antibodies, Monoclonal; D016207:Cytokines; C508572:IL18R1 protein, human; C508573:Il18r1 protein, mouse; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18