INTERLEUKIN-1-ALPHA AND COLLAGENASE ACTIVITY ARE ELEVATED IN CHRONIC WOUNDS

Interleukin-l-alpha (IL-1 alpha) is a member of a family of proinflamm atory polypeptide mediators that has been shown in vitro to stimulate collagenase production. Collagenase is a proteolytic enzyme classified as one of the matrix metalloproteinases (MMP-1) that specifically rec ognizes and cleaves collagen. Therefore, the objective of this study w as to compare the levels of these two proteins in chronic wounds as po ssible factors in the pathogenesis of chronic wounds. Fluids from 10 c hronic wounds were collected before and after a 1-week treatment with a hydroactive dressing (Cutinova cavity). In addition, fluids were col lected from 20 acute wounds for comparison. IL-1 alpha and MMP-1 level s were quantified using sandwich ELISA. Collagenase activity was measu red using a radiolabeled collagen as substrate. Clinically, the chroni c wounds showed decreased area (-21.0 cm(2)) and reduced volume (-134. 5 cm(3)) by 4 weeks after treatment with the hydroactive dressing. The re were no significant differences in the protein concentrations betwe en acute wound fluids (21.0 +/- 3.0 mg/ml) and chronic wound fluids be fore and after treatment with the hydroactive dressing (18.3 +/- 5.5 a nd 25.2 +/- 7.6 mg/ml, respectively). Levels of IL-1 alpha in the acut e wound fluids were low (0.019 pg/mg), whereas in the chronic wound fl uid before treatment they had been significantly elevated (44.9 +/- 21 .8 pg/mg). Following treatment with the hydroactive dressing, the IL-1 alpha levels dropped to 10.3 + 3.3 pg/mg (p < 0.05). Collagenase acti vity was not detectable in acute wound fluid, elevated in pretreatment chronic wounds (12.9 + 3.4 units), and decreased in chronic wounds af ter treatment (11.4 + 3.3 units). This study correlated clinical heali ng of chronic wounds with biochemical changes in the ulcer microenviro nment. As the chronic wounds began to heal, there was a significant de crease in the IL-1 alpha levels and collagenase activity, thus suggest ing that these two proteins may contribute to the lack of healing char acteristic of chronic wounds.