TABLE 3.

Pro- and anti-inflammatory cytokines secreted during tissue repair.

Pro-inflammatory cytokines	Cellular sources (immune system)	Effects on bone cells (bone resorption)	Reference
TNFα	Macrophages, T cells, NK cells, neutrophils, mast cells, B cells	→ Inhibit the differentiation and bone-forming activity of osteoblasts (OB) → Promote stromal cells to express RANKL for OC differentiation → Promote OC differentiation directly	Charatcharoenwitthaya et al. (2007), Reinke et al. (2013)
IL1, IL6	T cells, macrophages, monocytes	Up-regulate RANKL to promote OC differentiation	Greenblatt and Shim (2013), Mori et al. (2013)
IL17	T cells (Th17)	→ Acts on stromal cells and OB to up-regulate RANKL and OC differentiation	Lubberts et al. (2005), Tucci et al. (2013)
IFNγ	NK cells, T cells	→ Inhibit OC differentiation by down-regulating TRAF6 → Indirectly effect TNF and RANKL expression → Block OB differentiation by inhibiting induction of RUNX2, a master regulator of OB differentiation	Takayanagi et al. (2000), Mori et al. (2013)
Anti-inflammatory cytokines	Cellular sources (immune system)	Major effect on bone cells (bone formation)
IL4	T cells (Th2), mast cells, B cells, stromal cells	→ Inhibit OC differentiation → Inhibition of LPS-induced pro-inflammatory cytokine synthesis → Positively influence OB migration	Zaiss et al. (2007), Greenblatt and Shim (2013), Schmidt-Bleek et al. (2015)
IL10	Monocytes, T cells, type 1 regulatory T cells	→ Inhibit monocyte/macrophage and neutrophil cytokine production → Inhibit Th1-type lymphocyte response → Block NFκB pathway	Shouval et al. (2014)
IL35	Regulatory T cells, regulatory B cells	→ Suppress the proliferation of conventional T cells → Inhibit the differentiation of Th17 cells	Egwuagu and Yu (2015), Sun et al. (2015)
TGFβ	Constitutively expressed in many cell lines	→ Inhibit monocyte/macrophage MHC class II expression → Suppress proinflammatory cytokine synthesis MHC class II expression → Suppress pro-inflammatory cytokine synthesis	Schmidt-Bleek et al. (2015)