Potential application of immunotherapy for modulation of pulp inflammation: opportunities for vital pulp treatment

Abstract

Caries results in the demineralization and destruction of enamel and dentine, and as the disease progresses, irreversible pulpitis can occur. Vital pulp therapy (VPT) is directed towards pulp preservation and the prevention of the progression of inflammation. The outcomes of VPT are not always predictable, and there is often a poor correlation between clinical signs and symptoms, and the events occurring at a molecular level. The inflamed pulp expresses increased levels of cytokines, including tumour necrosis factor (TNF)a, interleukin (IL)-1a, IL-1b, IL-4, IL-6, IL-8, IL-17 and IL-23, which recruit and drive a complex cellular immune response. Chronic inflammation and sustained cytokine release can result in irreversible pulp damage and a decreased capacity for tissue healing.Other chronic inflammatory diseases, such as psoriasis, inflammatory bowel diseases and rheumatoid arthritis, are also characterized by an dysregulated immune response composed of relatively high cytokine levels and increased numbers of immune cells along with microbial and hard-soft tissue destructive pathologies. Whilst anti-cytokine therapies have been successfully applied in the treatment of these diseases, this approach is yet to be attempted in cases of pulp inflammation. This review therefore focuses on the similarities in the aetiology between chronic inflammatory diseases and pulpitis, and explores how anticytokine therapies could be applied to manage an inflamed pulp and facilitate healing. Further proof-ofconcept studies and clinical trials are justified to determine the effectiveness of these treatments to enable more predictable outcomes in VPT.

Present status and future directions—Vital pulp treatment and pulp preservation strategies

“…Early inflammatory defence responses generally resolve as a result of sclerosis and reactionary dentine deposition and if the balance is shifted regenerative events can be promoted (Cooper et al, 2014 ). More prolonged, intense inflammation may lead to a shift in the balance of events away from regeneration, and therefore, mechanisms should be developed which target inflammatory processes in the pulp such as pharmacological inhibitors (Al‐Natour et al, 2021 ) or immunotherapy (Arora et al, 2021 ). Finally, the capping material should evolve to target biological processes such as specific miRNA (Kearney et al, 2018 ), epigenetic processes (Duncan et al, 2016 ), anti‐oxidants (Minamikawa et al, 2011 ) or by direct application of growth factors (Tziafas et al, 1998 ), which may result in the promotion of higher quality regenerative rather than reparative responses in the dentin–pulp complex, improving scientific outcomes in the short term and potentially patients' outcomes in the long term.…”

The Role of microRNAs in Pulp Inflammation

“…A wide range of immune and non-immune cells in the pulp produce and secrete chemokines and cytokines, such as chemokine (C-C Motif) Ligand 2 (CCL2), CXCL1, CXCL2, CXCL8 (IL-8), CXCL10 IL-1α, IL-1β, IL-4, IL-6, IL-10, transforming growth factor (TGF)-1β, and tumor necrosis factor (TNF)-α, which are small glycoproteins (10 to 15 kD) that act as paracrine and autocrine molecular key agents because they regulate the recruitment, extravasation, activation, and differentiation of the immune cells of the pulp tissue [21][22][23]. During these inflammatory events, the nerve fibers of the peripheral nervous system are stimulated, which secrete many molecules, such as classical neurotransmitters (acetylcholine, glutamate, catecholamines), neuropeptides (substance P, calcitonin gene-related peptide, neuropeptide Y, neurokinin A), and excitatory amino acids, which contribute to the induction, sensitization, and maintenance of dental pain [24].…”

A critical review ofin vitroresearch methodologies used to study mineralization in human dental pulp cell cultures

“…Earlier intervention, before the pulp has become fully necrotic, offers opportunity for repair. Teeth with signs and symptoms indicative of reversible pulpitis still contain vital tissue and stem/progenitor cell populations and vital pulp therapies (VPTs), are therefore recommended (Arora et al, 2021 ; ESE, 2019 ). VPTs are included within regenerative endodontic procedures (REPs) targeted at salvaging the tissue and harnessing its natural capacity to repair hard and soft tissues.…”