Th1/Th17/Th22 immune response and their association with joint pain,imagenological bone loss,RANKL expression and osteoclast activity in temporomandibular joint osteoarthritis: A preliminary report

It is well accepted that the presence of cytokines belonging to the Th1/Th17/Th22 axis of immuno‐inflammatory response in the joint environment, such as IL‐1β, IL‐17 and IL‐22, respectively, are associated with pathogenesis of several synovial joint degenerative disorders. During temporomandibular joint osteoarthritis (TMJ‐OA), IL‐1β and IL‐17 have been implicated in the inflammation and resorption of sub‐chondral bone; however, the role of Th22 response in the TMJ‐OA pathophysiology has not been established. This study aimed to compare the expression of Th1/Th17/Th22‐type cytokines, chemokines and chemokine receptors in synovial fluid samples obtained from TMJ‐OA or disk displacement with reduction (DDWR) patients. In addition, it aimed to associate these levels with joint pain, imagenological signs of bone degeneration, RANKL production, osteoclastogenesis and osteoclast‐induced bone resorption. Higher levels of IL‐1β, IL‐17 and IL‐22 were expressed in TMJ‐OA compared with DDWR subjects, and these increased levels significantly correlated with RANKL expression, joint pain and articular bone degeneration. Higher levels of CCR5, CCR6 and CCR7, as well as their respective ligands CCL5 and CCL20, responsible for recruitment of IL‐1β, IL‐17 and IL‐22‐producing cells, were over‐expressed in TMJ‐OA compared with DDWR subjects. Osteoclastogenesis and osteoclast‐induced bone resorption were significantly greater in presence of synovial fluid from TMJ‐OA compared with DDWR subjects. These data demonstrate that cytokines, CCLs and CCRs associated with the Th1/Th17/Th22 axis of immuno‐inflammatory response are involved in TMJ‐OA pathogenesis. These findings suggest that IL‐22 is involved in the RANKL expression in TMJ‐OA, which in turn induces differentiation of osteoclasts and subsequent resorption of sub‐chondral bone.     

IL‐2/IL‐6 ratio correlates with liver function and recovery in acute liver injury patients

Acute liver injury can result from a number of different diseases. Inflammatory cytokines are known to be involved in the development of this condition; however, their precise roles and effects on liver function remain unclear. The goal of this study was to determine the relationship between serum cytokine levels and both the severity of liver damage and recovery in acute liver injury. We enrolled 100 patients with acute liver injury caused by drug application who were hospitalized from September 2012 to September 2017 and measured serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the cytokines, interleukin (IL)‐2 and IL‐6, before and after clinical therapy. Our results indicate that IL‐2 and IL‐6 levels are altered significantly following clinical therapy. However, with the exception of an association between IL‐2 and ALT, we found no correlation between the differences in cytokine levels pre‐ and post‐therapy and recovery of liver function. In contrast, we observed that pre‐ vs post‐treatment difference in the IL‐2/IL‐6 ratio negatively correlates with the pre‐ vs post‐treatment difference in ALT and AST values, and positively correlates with ALT and AST at 1‐month post‐discharge. Thus, our data suggest that IL‐2/IL‐6 ratio may represent a novel predictor for the prognosis of liver injury.     

Effect of single‐dose injection of vitamin D on immune cytokines in ulcerative colitis patients: a randomized placebo‐controlled trial

Ulcerative colitis (UC) is a chronic recurrent inflammation of the colon. It has been proposed that the UC pathogenesis may be related to vitamin D deficiency and/or vitamin D administration in UC patients may have an ameliorating effect on the intestinal inflammation. The aim of this study was to assess the effect of vitamin D on the serum levels of immune cytokines in UC patients. In this double‐blind randomized controlled trial, 90 mild‐to‐moderate UC patients were assigned to get either a single muscular injection of 7.5 mg vitamin D3 or 1 mL normal saline as placebo. Three months later serum levels of IL‐4, IL‐10, IL‐12p70, IFN‐γ, and TNF‐α were measured. Two group variables were compared using independent t‐test and analysis of covariance (ANCOVA). There was a significant increase in vitamin D only in the vitamin D group. Compared to placebo, vitamin D had significant decreasing effects on serum TNF‐α, IFN‐γ, and IL12p70 levels, but it had no significant effect on serum levels of IL4 and IL10. Vitamin D seems to inhibit Th1 immune responses and have no effect on Th2 responses. The findings of this study support several in vitro studies, which suggest a therapeutic immunomodulatory potential of vitamin D.     

Plasma matrix metalloproteinase 7, CC-chemokine ligand 18, and periostin as markers for pulmonary sarcoidosis

BackgroundSome patients with sarcoidosis experience worsening of pulmonary lesions. However, no biomarker has been identified that reflects pulmonary disease status in sarcoidosis. We investigated the usefulness of potential markers of pulmonary fibrosis in patients with sarcoidosis.MethodsPlasma matrix metalloproteinase 7 (MMP-7), CC-chemokine ligand 18 (CCL-18), and periostin levels were evaluated in 60 patients with sarcoidosis and 30 healthy controls; bronchoalveolar lavage fluid levels were analyzed in 22 patients with sarcoidosis. To determine the usefulness of these markers, we explored potential correlations between these markers and sarcoidosis clinical characteristics.ResultsPlasma MMP-7, CCL-18, and periostin concentrations were significantly higher in patients with sarcoidosis than those in healthy controls. MMP-7 concentrations in plasma and bronchoalveolar lavage fluid were higher in patients with sarcoidosis with parenchymal infiltration than in those without lung lesions. Moreover, MMP-7 concentration was negatively correlated with pulmonary function.ConclusionAmong these novel biomarkers, MMP-7 most precisely reflected pulmonary sarcoidosis disease status and thus, might be useful for diagnosing and evaluating sarcoidosis, particularly in patients with pulmonary parenchymal lesions.     

Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches

Atopic dermatitis (AD) is a chronic, systemic, inflammatory disease that affects the skin and is characterized by persistent itch and marked redness. AD is associated with an increased risk of skin infections and a reduced quality of life. Most AD treatment options to date were not designed to selectively target disease‐causing pathways that have been established for this indication. Topical therapies have limited efficacy in moderate‐to‐severe disease, and systemic agents such as corticosteroids and immunosuppressants present with tolerability issues. Advances in the understanding of AD pathobiology have made possible a new generation of more disease‐specific AD therapies. AD is characterized by the inappropriate activation of type 2 T helper (Th2) cells and type 2 innate lymphoid (ILC2) cells, with a predominant increase in type 2 cytokines in the skin, including interleukin (IL)‐13 and IL‐4. Both cytokines are implicated in tissue inflammation and epidermal barrier dysfunction, and monoclonal antibodies targeting each of these interleukins or their receptors are in clinical development in AD. In March 2017, dupilumab, a human anti–IL‐4Rα antibody, became the first biologic to receive approval in the United States for the treatment of moderate‐to‐severe AD. The anti–IL‐13 monoclonal antibodies lebrikizumab and tralokinumab, which bind different IL‐13 epitopes with potentially different effects, are currently in advanced‐stage trials. Here, we briefly review the underlying pathobiology of AD, the scientific basis for current AD targets, and summarize current clinical studies of these agents, including new research to develop both predictive and response biomarkers to further advance AD therapy in the era of precision medicine.