Characterization of IL-1 inhibitory factor released from human alveolar macrophages as IL-1 receptor antagonist

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Abstract
IL‐1 possesses pleiotropic properties on various cells and its activity may be stringently regulated in several ways. We have previously reported that both IL‐1 and its inhibitory factor are concomitantly released from alveolar macrophages in both healthy subjects and patients with chronic inflammatory lung diseases. An increase in IL‐1 activities and a decrease in inhibitory activities arc characteristics found in both healthy smokers and patients with interstitial lung diseases. In this study, we further examined the biological properties of IL‐1 inhibitory factor. The inhibitor exhibited a dose‐dependent specific inhibition of an augmentation by IL‐1 of PH‐nduced murinc thymocyte proliferation, while no inhibition of the augmentation by IL‐2, IL‐4, IL‐6, or tumour necrosis factor (TNF) was found. 125I‐labelled IL‐1α binding on PHA‐stimulated murinc thymocytes revealed two types of IL‐1 binding sites. 44 sites/cell with a Kd of 2.7 ± 10−10 m and 230 sites/cell with a Kd of 2.5 ± 10−9 m. Alveolar macrophage culture supernatants blocked the binding of labelled IL‐1 to the IL‐1 receptor in a dos‐ependent fashion. Scatchard plot analysis revealed that the inhibitory factor in the supernatants blocked the binding competitively. These results indicate that alveolar macrophages produce a specific IL‐1 inhibitory factor, functioning as an IL‐1 receptor antagonist.