The Physiopathological Role of IL-33: New Highlights in Bone Biology and a Proposed Role in Periodontal Disease

Table 1

Role of IL-1 cytokine family members in tissue repair/fibrosis and osteoclastogenesis.

Common name	IL-1 family name	Cell type present	Role in tissue repair and fibrosis during inflammation	Role in osteoclastogenesis
IL-1𝛼 [1, 22]	IL-1F1	(i) Keratinocytes, thymic epithelium, hepatocytes, endothelial cells, fibroblasts, epithelial cells of mucus membranes (intracellular) [23]; (ii) Lymphocytes or macrophages activated [23, 24]	(i) Role in the early stages of inflammation [32]; (ii) Leukocyte recruitment by endothelial cells [32]; (iii) Fibroblasts proliferation and collagen synthesis [32]	Activation of osteoclasts [22]
IL-1𝛽 [1, 22, 32]	IL-1F2	(i) Monocytes, macrophages, dendritic cells (DC), B lymphocytes, NK cells [22, 32]; (ii) Gingival fibroblasts [30, 33]; (iii) Macrophages, monocytes [24, 32]; (iv) Th1 lymphocyte [32]; (v) Osteoblasts [31]	(i) Regulates the production of metalloproteinases [30, 33]; (ii) Induction and proliferation of fibroblasts and collagen [30, 33]; (iii) Stimulates the release of PDGF and TGF-𝛽 [30, 35]; (iv) Fibroblast proliferation and collagen synthesis [30, 33]	(i) Differentiation and activation of osteoclast [22, 24]; (ii) Increases synthesis of collagenase [22]; (iii) Increases bone resorption [22]
IL-1Ra [1, 15, 16, 27]	IL-F3	Macrophages [27]	(i) Pleiotropic actions [27]; (ii) Inhibits the production of metalloproteinases (MMPs) [30, 33]	Blocks the activation of osteoclasts [31]
IL-33 [1]	IL-F11	(i) Endothelial and epithelial cells [2]; (ii) Macrophages [15]; (iii) Neutrophils [14]; (iv) Basophiles [12, 13]; (v) Eosinophils [11, 12]; (vi) Th2 cells, mast cells, osteoblasts, and osteoclast [1, 19, 20]	(i) In physiological conditions are in balance, maintaining the structure of the tissue [39]; (ii) Stimulates the formation of collagen and a protective function against infections [14]; (iii) Produced by Th2-phenotype cells [9]; (iv) Anti-inflammatory response as the augmentation of Th2 response [37]	(i) Monocyte differentiation into osteoclasts [40]; (ii) Leading to the production of RANKL and diminishing the production of OPG and subsequent activation of osteoclasts [40]; (iii) Inhibits the TNF-𝛼-induced bone destruction via IL-33/ST2 axis [38]