Effects of Calcium Hydroxide Intracanal Medications on T Helper (Th1, Th2, Th9, Th17, and Tfh) and Regulatory T (Treg) Cell Cytokines in Apical Periodontitis: A CONSORT RCT.

INTRODUCTION: This Consolidated Standards of Reporting Trials randomized clinical trial investigated T helper (Th1, Th2, Th9, Th17, and Tfh) and regulatory T (Treg) cell-type cytokines and their networks in apical periodontitis (AP). We also assessed the effects of calcium hydroxide [Ca(OH)2] intracanal medications (ICMs) on helper T and Treg cell-type cytokines. METHODS: Twenty teeth with primary endodontic infection and apical periodontitis were randomly divided into two groups: Ca(OH)2 + saline solution (n = 10) and Ca (OH)2 + 2% chlorhexidine-gel (n = 10). Samples were collected from the periradicular tissue fluid (PTF) before (PTFs1) and after 14 days of ICMs (PTFs2). The Human High Sensitivity T Cell Panel was used to quantify target T-helper (Th)1: interelukin (IL)-2, IL-12, and interferon-gamma (IFN-γ); Th2: IL-4, IL-5, and IL-13; Th9: IL-9; Th17: IL-17; T follicular helper cells (Tfh): IL-21; and Treg-cell-type cytokine: IL-10. RESULTS: Th1-type cytokines were higher than Th2-type ones, at PTFs1. Positive (+) associations were found among all Th1-type cytokines and all Th2-type cytokines. There were negative (-) correlations between all Th1- and Th2-type cytokines. Size of radiolucent lesions and symptoms (tenderness to percussion and/or pain on palpation) were positively correlated with Th1-type cytokines, IL-17, and IL-21 but negatively correlated with Th2-type cytokines and IL-10 (all, P < .001). Both ICMs increased Th2-type cytokines and IL-10 (P < .05) and decreased Th1-type cytokines, IL-17, and IL-21 (P < .05), with no differences among them (P > .05). CONCLUSIONS: Complex T-cell cytokine networks are involved in AP. Both Ca(OH)2 ICMs effectively increased IL-4, IL-5, IL-10, and IL-13 and lowered IL-2, IL-12, IL-17, IL-21, and IFN-γ.

Clinical influence of calcium hydroxide intracanal medications on matrix metalloproteinases and tissue inhibitors of metalloproteinases in apical periodontitis.

OBJECTIVES: This study investigated the influence of calcium hydroxide intracanal medications on the levels of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in apical periodontitis (AP). MATERIALS AND METHODS: Twenty primarily infected root canals with AP were randomly divided into two groups: Ca(OH)2 + sterile saline solution (SSL) group and Ca(OH)2 + 2% chlorhexidine gel (CHX gel) group. We collected samples from the periradicular tissue fluid (PTF) before (s1) and after 14 days of intracanal medication (s2). MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured by ELISA assay. RESULTS: MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were detected in all PTF samples at s1 and s2 (20/20). At s1, MMP-2 and MMP-9 were detected at higher levels than MMP-1 (p < .05). Higher levels of TIMP-1 than TIMP-2 were found in AP (p < .05). Additionally, we detected higher MMP-1, MMP-2, and MMP-9 over TIMP-1 and TIMP-2 levels in AP (p < .05). At s2, Ca(OH)2 + SSL was as effective as Ca(OH)2 + 2% CHX gel in lowering the levels of MMP-1, MMP-2, and MMP-9 after 14 days of intracanal medication, with no significant difference between them (p > .05). Both Ca(OH) 2 intracanal medications had no significant impact on the levels of TIMP-1 and TIMP-2 (both p > .05). At s2, TIMP-1 levels were higher than TIMP-2 (p < .05). Moreover, there were positive correlations between the levels of MMP-1 and TIMP-1 and MMP-1 and TIMP-2 (p < .05). CONCLUSIONS: Calcium hydroxide medications effectively lowered the levels of MMP-1, MMP-2, and MMP-9 in periapical tissues after 14 days of treatment, with no difference between them. Moreover, the calcium hydroxide intracanal medications tested here had no impact in TIMP-1 and TIMP-2 in periapical tissues. CLINICAL RELEVANCE: MMPs and TIMPs play an essential role in the degradation of the extracellular matrix. The imbalance MMPs and TIMPs can cause periapical tissue destruction. Therefore, the reestablishment of the balance between activated MMPs and TIMPs with root canal therapy is essential to restore tissue homeostasis.

Clinical Investigation of Matrix Metalloproteinases, Tissue Inhibitors of Matrix Metalloproteinases, and Matrix Metalloproteinase/Tissue Inhibitors of Matrix Metalloproteinase Complexes and Their Networks in Apical Periodontitis.

INTRODUCTION: This clinical study investigated the levels of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and respective forms (MMP/TIMP complexes) in apical periodontitis to determine their networks in the development of clinical/radiographic features, thus quantifying the levels of endotoxins (lipopolysaccharides) present in primarily infected root canals with apical periodontitis. METHODS: Twenty primarily infected root canals with apical periodontitis were selected. The presence of pain on palpation, tenderness to percussion, and the size of the radiographic lesion were recorded. The levels of MMPs (MMP-1, -2, and -9), TIMPs (TIMP-1 and -2), and their MMP/TIMP complexes (MMP-1/TIMP-1, MMP-1/TIMP-2, MMP-2/TIMP-1, MMP-2/TIMP-2, MMP9/TIMP-1, and MMP-9/TIMP-2) present in the periapical interstitial fluid were measured using the enzyme-linked immunosorbent assay. The kinetic chromogenic LAL test was used to quantify endotoxins. RESULTS: A higher mean level of MMP-9 (968.35 ± 342.00 pg/mL) was followed by MMP-2 (894.00 ± 591.62 pg/mL) and MMP-1 (789.43 ± 342.83 pg/mL). The linear regression analysis revealed a positive association of MMP-1 with both MMP-2 and MMP-9 (all P < .001). TIMP-1 (481.79 ± 86.09 pg/mL) (24/24) was found in higher levels than TIMP-2 (206.45 ± 86.09 pg/mL) (P < .05), including a positive correlation of MMP-1 with both TIMP-1 and TIMP-2 (all P < .05). Higher mean levels of MMP1, -2, and -9 were found in teeth with larger-size radiolucent lesions (>7 mm) compared with smaller ones (≤7 mm) (all P < .01). Higher levels of MMP-1 decreased the chance of TTP, whereas MMP-9 (odds ratio = 0.97) increased the chance of pain on percussion (odds ratio = 1.01). Higher levels of endotoxins present in root canals were positively correlated with larger amounts of MMP -9 (P < .05). CONCLUSIONS: MMPs, TIMPs, and their complexes (MMP/TIMP) are involved in apical periodontitis by interacting with complex networks in the development of clinical features and the severity of bone destruction.