Glucan phosphate treatment attenuates burn-induced inflammation and improves resistance to Pseudomonas aeruginosa burn wound infection.
These studies evaluated the effects treatment with glucan phosphate, a soluble polysaccharide immunomodulator, on the inflammatory response induced by burn injury and on resistance to Pseudomonas aeruginosa burn wound infection. Mice were exposed to 35% total body surface area burns and were resuscitated with lactated Ringer's (LR) solution alone or LR supplemented with glucan phosphate (40 mg/kg). Glucan phosphate treatment attenuated burn-induced expression of interleukin (IL)-1beta, IL-6, and IL-10 mRNAs in spleen, lung, and heart. Plasma concentrations of IL-1beta, IL-6, macrophage inflammatory protein (MIP)-2, and IL-10 were also decreased in burned mice treated with glucan phosphate compared with vehicle-treated controls. Early postburn mortality was not significantly different between control (20%) and glucan phosphate-treated (10%) mice, but there was a small improvement in acid-base balance in the glucan phosphate-treated group. Mice received a second injection of glucan phosphate or LR on day 4 postburn and were infected by topical application of P. aeruginosa to the burn wound on day 5. Glucan phosphate treatment significantly improved survival in mice exposed to P. aeruginosa burn wound infection. The improved survival correlated with lower bacterial burden in the burn wound, attenuated production of proinflammatory cytokines, and enhanced production of Th1 cytokines. These studies show that glucan phosphate treatment attenuates burn-induced inflammation and increases resistance to P. aeruginosa burn wound infection in an experimental model of burn injury.
Lyuksutova
Olga I
OI
Department of Anesthesiology, University of Texas Medical Branch and Shriners Hospital for Children, 301 University Boulevard, Galveston, TX 77555, USA.
Murphey
Erle D
ED
Toliver-Kinsky
Tracy E
TE
Lin
Cheng Y
CY
Cui
Weihua
W
Williams
David L
DL
Sherwood
Edward R
ER
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D002056:Burns / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005936:Glucans / Q000627:therapeutic use*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control*; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014946:Wound Infection / Q000517:prevention & control*
D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D005936:Glucans; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; C480175:glucan phosphate; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma