Semapimod reduces the depth of injury resulting in enhanced re-epithelialization of partial-thickness burns in swine.
Studies suggest that tumor necrosis factor alpha (TNF-alpha) plays a role in burn pathogenesis. We conducted a randomized controlled experiment in swine to determine whether a novel macrophage inhibitor, semapimod (formerly known as CNI-1493), would blunt the local production of TNF-alpha, interleukin (IL)-1, and IL-6 in burns leading to less injury extension and faster re-epithelialization. After creating second-degree burns, animals received one or two intravenous boluses of semapimod 1 mg/kg or normal saline, and all burns were treated with silver sulfadiazine. The depth of follicular necrosis and thrombosis was reduced by either one or two doses of semapimod (P=.04 and .02, respectively). However, no differences were noted between groups in cytokine levels. Depth of scarring was similar in all groups. We conclude that Semapimod reduces the depth of follicular necrosis and thrombosis after second-degree burns in swine, indirectly resulting in more rapid re-epithelialization. However, this affect does not appear to be mediated by reduced local TNF-alpha, IL-1, or IL-6 protein levels.
Department of Emergency Medicine, Stony Brook University, Stony Brook, New York 11794-8350, USA.
Adam J
AJ
Singer
Steve A
SA
McClain
Gabriele
G
Hacht
Galina
G
Batchkina
Marcia
M
Simon
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D001458:Bandages; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism; D002921:Cicatrix / Q000473:pathology; D004817:Epidermis / Q000378:metabolism; D005260:Female; D018859:Hair Follicle / Q000473:pathology; D006835:Hydrazones / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007262:Infusions, Intravenous; D009336:Necrosis; D011897:Random Allocation; D012837:Silver Sulfadiazine / Q000494:pharmacology; D013552:Swine; D013927:Thrombosis / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D000813:Anilides; D006146:Guanidines
D000891:Anti-Infective Agents, Local; D006835:Hydrazones; D007166:Immunosuppressive Agents; D012837:Silver Sulfadiazine; D014409:Tumor Necrosis Factor-alpha; C097256:semapimod; D000813:Anilides; D006146:Guanidines