Resolution of Sterile Inflammation: Role for Vitamin C

Abstract

Introduction. Macrophage reprogramming is vital for resolution of acute inflammation. Parenteral vitamin C (VitC) attenuates proinflammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inflammation is limited. Methods. To examine whether physiological levels of VitC modulate resolution of inflammation, we used transgenic mice lacking L-gulono-γ-lactone oxidase. VitC sufficient/deficient mice were subjected to a thioglycollate-elicited peritonitis model of sterile inflammation. Some VitC deficient mice received daily parenteral VitC (200 mg/kg) for 3 or 5 days following thioglycollate infusion. Peritoneal macrophages harvested on day 3 or day 5 were examined for intracellular VitC levels, pro- and anti-inflammatory protein and lipid mediators, mitochondrial function, and response to lipopolysaccharide (LPS). The THP-1 cell line was used to determine the modulatory activities of VitC in activated human macrophages. Results. VitC deficiency significantly delayed resolution of inflammation and generated an exaggerated proinflammatory response to in vitro LPS stimulation. VitC sufficiency and in vivo VitC supplementation restored macrophage phenotype and function in VitC deficient mice. VitC loading of THP-1 macrophages attenuated LPS-induced proinflammatory responses. Conclusion. VitC sufficiency favorably modulates macrophage function. In vivo or in vitro VitC supplementation restores macrophage phenotype and function leading to timely resolution of inflammation.

Evaluation of the Anti-Inflammatory Effect of Locally Delivered Vitamin C in the Treatment of Persistent Gingival Inflammation: Clinical and Histopathological Study

“…Moreover, in order to reach this dose at the site of inflammation, administration of very high systemic doses is needed, which could be harmful to the patient. The local injection provides the needed dose efficiently [21]. …”

Vitamin C promotes wound healing through novel pleiotropic mechanisms

“…Blood samples obtained from mice on days 7 and 14 post‐wounding were kept on ice, centrifuged and the resultant plasma was deproteinised as previously described . Briefly, 100 µl of plasma was deproteinised with 200 µl of cold 20% trichloroacetic acid (TCA), and treated with 200 µl of cold 0·2% dithiothreitol (DTT) to prevent oxidation.…”

“…Moreover, scorbutic individuals experience delayed healing and decreased rates of collagen synthesis and maturation . Along with its strong antioxidant properties, VitC is an essential co‐factor for multiple enzymatic reactions and has recently been shown to suppress pro‐inflammatory processes by pleiotropic mechanisms while promoting anti‐inflammatory and pro‐resolution effects in macrophages . VitC is also intimately involved in collagen metabolism and regulation and therefore many studies have focused on its particular role in wound healing .…”

Role of vitamin C in wound healing after dental implant surgery in patients treated with bone grafts and patients with chronic periodontitis

“…17,18 Vitamin C can decrease the responses of some inflammatory biomarkers, including C-reactive protein, and several pro-inflammatory cytokines such as tumor necrosis factor, interferons, and interleukins. 17,18 Vitamin C can decrease the responses of some inflammatory biomarkers, including C-reactive protein, and several pro-inflammatory cytokines such as tumor necrosis factor, interferons, and interleukins.…”

“…Vitamin C is an important cofactor for several enzymatic reactions occurring in the body, and it can promote anti-inflammatory progression through multipotent mechanisms in macrophages. 17,18 Vitamin C can decrease the responses of some inflammatory biomarkers, including C-reactive protein, and several pro-inflammatory cytokines such as tumor necrosis factor, interferons, and interleukins. 19 In addition, vitamin C can influence the wound-healing genes, such as inhibiting the activation of nuclear factor kappa-light-chain-enhancer of activated B cells and endothelial cells, which play important roles in the regulation of gene expression during inflammation.…”