Effect of recombinant human granulocyte-macrophage colony-stimulating factor on expression of metalloproteinases and tissue inhibitors of metalloproteinase in residual burn wounds

Abstract

Objective To investigate the effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the expression of metalloproteinases (MMP)-1, MMP-2, MMP-13 and tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 in residual burn wounds. Methods The study was a randomized and self-controlled clinical trial. Ten patients with residual burn wounds were selected. Two residual burn wounds with area of 16-25 cm2 were selected from every patient and were divided into combined group (with treatment of rhGM-CSF gel and mupirocin ointment) and control group (with treatment of mupirocin ointment) randomly. The wound healing rate at the 7th and 14th day after treatment and wound healing time were investigated. The wound tissue samples around the wounds before remedy and at the 7th and 14th day after remedy were obtained for evaluation of expression change of MMP-1, MMP-2, MMP-13, TIMP-1 and TIMP-2 by immunohistochemistry. Results The wound healing rate in combined group was (42±7)% and (86±6)% respectively at the 7th and 14th day after remedy, which was obviously higher than that in control group [ (35±8)%, t=16.927, P=0.000; (68±7)%, t=41.849, P=0.000]. The average wound healing time was (17.8±1.5) days in combined group, which was significantly shorter than that in control group [ (21.1±1.6) days, t=-21.604, P=0.000]. Before remedy, the differences of MMP-1, MMP-2, TIMP-1 and TIMP-2 measured of two groups were not significant. At the 7th and 14th day after remedy, the integral optical density (IA) of MMP-1 (2 128±157 and 1 644±157 respectively) and MMP-2 (1 834±130 and 1 493±105 respectively) in the combined group were significantly decreased compared with control group (MMP-1: 3 653±181 and 3 060±175; MMP-2: 2 350±121 and 2 064±109) respectively. The IA of TIMP-1 (855±120 and 1 187±125 respectively) and TIMP-2 (773±117 and 1 039±134 respectively) in the combined group were significantly increased compared with control group (TIMP-1: 590±111 and 846±101; TIMP-2: 614±91 and 808±124) respectively. The expression of MMP-13 was not measured in two groups before and after remedy. Conclusion The healing-promoting effect of rhGM-CSF on residual burn wounds may be in association with inhibiting the expression of MMP-1 and MMP-2 or inducing the expression of TIMP-1 and TIMP-2 in wound tissue. Key words: Burns; Granulocyte-macrophage colony-stimulating factor; Wound healing; Metalloproteinases