Inhalation of Carbon Monoxide Ameliorates Collagen-induced Arthritis in Mice and Regulates the Articular Expression of IL-1β and MCP-1

Abstract

Carbon monoxide (CO), long considered a toxic gas, has recently been shown to mediate anti-inflammatory effects in various animal models. The aim of this study was to investigate whether the inhalation of CO ameliorated collagen-induced arthritis (CIA) in mice. CIA was induced in female DBA/1 mice by the injection of an anti-type II collagen antibody and lipopolysaccharide. The CO treatment group was exposed to CO gas at a concentration of 200 ppm in a closed cage starting on the day of the injection with an anti-type II collagen antibody and throughout the remaining study period. The clinical arthritis scores was examined daily for swelling of the paws as a sign of arthritis. For histopathology, the sections of the hind legs were evaluated by hematoxylin-eosin staining. Moreover, we evaluated the expression of interleukin (IL)-1beta and monocyte chemoattractant protein-1 (MCP-1) mRNA in the hind paws. Both clinical arthritis scores as well as histological findings of joint inflammation were significantly reduced in mice treated with CO gas inhalation compared to untreated mice. Further, CO significantly inhibited the increased expression of IL-1beta and MCP-1 mRNA in paws at day 3 after the induction of arthritis. In conclusion, the inhalation of CO protected mice from the synovial inflammation of CIA. Based on these data, the beneficial effects of CO in murine RA model may be attributed to its anti-inflammatory properties.

Carbon monoxide inhibits T cell activation in target organs during systemic lupus erythematosus

“…Furthermore, we have described recently that both SLE patients, as well as lupus-prone mice, show a decreased expression of HO-1 in peripheral blood monocytes [14,15]. During immune-mediated diseases, such as MS, type 1 diabetes, collagen induced arthritis (CIA) and organ transplant rejection, several immunoregulatory functions have been attributed to CO, which is an HO-1 product [16][17][18][19]. Along these lines, we have recently reported that CO exposure prevents both monocyte population expansion and the decline of regulatory T cells (T regs ) in hybrid FcgRIIb knock-out (KO) mice, which develop a mild lupus-like syndrome [15].…”

Carbon Monoxide Liberated from Carbon Monoxide-Releasing Molecule Exerts an Anti-inflammatory Effect on Dextran Sulfate Sodium-Induced Colitis in Mice

“…Interestingly, recent evidence suggests that providing exogenous CO suppresses the inflammatory response associated with various disease states and conditions such as hyperoxia [10], organ transplantation, ischemia-reperfusion injury [11][12][13][14], and inflammation [15,16]. In intestinal inflammation, exogenous CO also reduces the severity of disease activity [17,18].…”

The Therapeutic Potential of Carbon Monoxide for Inflammatory Bowel Disease

“…Potent therapeutic efficacies of CO have been demonstrated in experimental models of several conditions, including lung injuries [35], heart, hepatic and renal I-R injuries [19,36,37], as well as inflammation, including arthritis [38], supporting the new paradigm that CO at low concentrations functions as a signaling molecule that exerts significant cytoprotection and anti-inflammatory actions. Similar to what has been observed for the therapeutic effects of CO against various diseases, CO has been reported to mediate potent cytoprotective and anti-inflammatory effects in in vivo colitis models (table 1).…”