Table 1.

Brief overview of pro-inflammatory cytokines involved in periodontal disease.

Cytokine	Pro-inflammatory action
IL-1	Is involved in both innate and adaptive immune responses, activates T lymphocytes by enhancing the
	production of IL-2 [A], augments B-cell proliferation, increases immunoglobulin synthesis, stimulates
	endothelial cell adherence of leukocytes, induces periodontal bone loss stimulated by pathogens [B].
IL-1α	Assists IL-23 and IL-6 in the activation of Th17 and the expression of IL-17 [A].
IL-1β	Is induced upon host-microbiota interaction and leads the activation of both Th1 and Th2 cells; is involved
	in the inflammatory cell migration and stimulation of bone resorption [A,C].
IL-2	Is implicated in the Treg cells and NK cell activation and B and T cell promotion and differentiation [A,B].
IL-5	Promotes accumulation of eosinophils through its ability to upregulate responses to chemokines, enhances
	cytotoxicity, prolongs eosinophil survival at inflammation sites by blocking apoptosis, also induces maturation
	of cytotoxic T lymphocytes and basophilic differentiation [A,B].
IL-6	Participates in the Th17 cell-induced differentiation of CD4+ T cells, associated with inflammatory cell
	migration and [B,D], is implicated in bone homeostasis through upregulation expression of the receptor
	activator RANKL in osteoblasts, leading to osteoclast differentiation and bone resorption [C,D].
IL-7	Is implicated in the development of B and T lymphocytes, stimulates the proliferation and differentiation
	of cytotoxic T cells and NK cells, stimulates the tumoricidal activity of monocytes and macrophages [B].
IL-9	Supports the growth of antigen-specific T lymphocytes and regulates some hematopoietic cells [B].
IL-12	Promotes IFN-γ production in T cells and NK for bacterial clearance, activates and induces proliferation,
	cytotoxicity, as well as cytokine production of NK cells; IL-12 mediates the clearance of local bacteria,
	inhibits bone resorption displaying, also protective effects in the pathogenesis of PD [B,D].
IL-17	Recruits and activates cells of the innate immune response, upregulates antimicrobial factor expression
	leading to dysbiotic microbiome promotion [D,E], exerts protective effects on the local mucosal barrier [A].
	IL-17 is also associated with chronic inflammatory tissue destruction and alveolar bone loss [B,C].
IL-18	Is an IFN-γ-inducing factor, and an activator of Th1 and NK cells, stimulating the expression of MMPs [C,D].
	IL-18 overexpression is related to inflammatory bone loss after P. gingivalis infection, also drives the
	polarization and activation of antigen-specific lymphocytes and myeloid cells under microbial challenge [D].
IL-23	Is a member of the IL-12 family, secreted by myeloid antigen presenting cells exposed to P. gingivalis and
	periodontal ligament fibroblasts stimulated by IL-1β [B,C]. Promotes the pathogenicity of Th17 cells and
	the suppression of anti-inflammatory IL-10 [B].
IL-33	Is involved in the modulation of Th2 cells, related to periodontal bone loss [B,C,D], drives the differentiation,
	polarization and activation of antigen-specific lymphocytes and myeloid cells under microbial challenge [D].
IFN-γ	Stimulates antigen presentation and cytokine production by monocytes, stimulates the accumulation of
	macrophages [B,D,E], killing intracellular pathogens and clearing infections [F] by NK cells and neutrophils.
	IFN-γ is also related to periodontal tissue destruction [D].
TNF	Participates in bone metabolism, exacerbating bone resorption and damaging the oral mucosal barrier [B,C].
	TNF-α plays a central role in the phagocyte cell activation and endotoxic shock [F], loss of connective tissue
	attachment and up-regulates the production of classic pro-inflammatory innate immunity cytokines [E].
	Along with IL-1β is associated with inflammatory cell migration and osteoclastogenesis processes [D].

IL, interleukins; Th, T helper; Treg, regulatory T cells; NK, natural killer; RANKL, receptor activator of nuclear factor-kB ligand; IFN-γ, interferon-γ; MMPs, matrix metalloproteinases; TNF, tumor necrosis factor; Reference sources: [A]: Pan et al. (2019), [B]: Borish and Steinke (2003), [C]: Ramadan et al. (2020), [D]: Garlet (2010), [E]: Graves (2008). [F] Turner et al. (2014).