Therapeutic effects of vitamin D and IL-22 on methotrexate-induced mucositis in mice.

Mucositis is a common side effect of cancer therapies and transplant conditioning regimens. Management of mucositis involves multiple approaches from oral hygiene, anti-inflammatory, anti-apoptotic, cytoprotective, and antioxidant agents, to cryo-therapy, physical therapy, and growth factors. There is room for novel, affordable treatment options, or improvement of currently available therapies. Vitamin D has been shown to regulate mucosa-resident cell populations such as Th17 or innate lymphoid cells and critical mucosal cytokine IL-22; however, their therapeutic potential has not been put to test in preclinical mouse models. In this study, we aimed to test the therapeutic potential of vitamin D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Balb/c mice were given daily intraperitoneal injections of vitamin D. Mucositis was induced by methotrexate. Another group received IL-22 plasmid via hydrodynamic gene delivery. Weight loss and intestinal histopathology, intestinal levels of cytokines IL-22, IL-17A, GM-CSF, IL-23, IFN-γ, TNF-α, and IL-10, and number of intestinal lamina propria B cell, neutrophil, and total innate lymphoid cells were quantified. Daily vitamin D injections ameliorated intestinal inflammation and elevated intestinal IL-22 levels compared with control groups. Temporal overexpression of IL-22 by hydrodynamic gene delivery slightly increased intestinal IL-22 but failed to confer significant protection from mucositis. To our knowledge, this is the first experimental demonstration in an animal model of mucositis of therapeutic use of vitamin D and IL-22 supplementation and our results with vitamin D suggest it may have merit in further trials in human mucositis patients.

Protective effect of vitamin D against hyperoxia-induced lung injury in newborn rats.

INTRODUCTION: Preterm infants have risks of developing vitamin D deficiency. Thus we aimed to investigate the effect of vitamin D on hyperoxia-induced lung injury in newborn rats. METHODS: Full term rat pups were included in the study 12-24 hr after delivery. The pups were randomly divided into eight groups as follows: normoxia control group (NC), normoxia plus vitamin D group (ND1, 1 ng/gr/day vitamin D), normoxia plus vitamin D group (ND2, 3 ng/gr/day vitamin D), normoxia plus vitamin D group (ND3, 5 ng/gr/day vitamin D), hyperoxia control group (HC), hyperoxia plus vitamin D group (HD1, 1 ng/gr/day vitamin D), hyperoxia plus Vitamin D group (HD2, 3 ng/gr/day vitamin D), hyperoxia plus vitamin D group (HD3, 5 ng/gr/day vitamin D). The histopathological effects of vitamin D were assessed by alveolar surface area (with mean linear intercept (MLI) method), apoptosis index and proliferating cell nuclear antigen (PCNA) index. RESULTS: MLI values were significantly lower among three groups (HD1: 83.93 ± 1.95 µm, HD2: 81.76 ± 1.68 µm, and HD3: 82.33 ± 1.87 µm) when compared with HC group (92.98 ± 2.09 µm) (P = 0.001, P = 0.0004, P = 0.002, respectively). Apoptotic cell index were significantly lower among three treatment groups (HD1: 1.455 ± 0.153, HD2: 0.575 ± 0.079, and HD3: 0.700 ± 0.105) when compared with HC group (2.500 ± 0.263) (P = 0.001, P = 0.001, P = 0.001, respectively). Although PCNA positive cell index did not change in HD1 group (0.132 ± 0.008) (P > 0.05), there were significant increases in HD2 (0.277 ± 0.026) and HD3 (0.266 ± 0.018) group when compared with HC group (0.142 ± 0.010) (HD2 P = 0.001, HD3 P = 0.001). CONCLUSION: Vitamin D seems to protect hyperoxia-induced lung injury in newborn rats. Pediatr Pulmonol. 2017;52:69-76. © 2016 Wiley Periodicals, Inc.