In vivo characterization of interleukin-4 as a potential wound healing agent

Interleukin-4 increases the synthesis of extracellular matrix proteins, including types I and III collagen and fibronectin, by both human and rat fibroblasts. Because fibroblasts are the final common effector cells of most phases of tissue repair, this study set out to investigate the effects of interleukin-4 on the healing of three different types of wounds. Acute excisional and chronic granulating wounds inoculated with Escherichia coli and incisional wounds in streptozotocin-induced diabetic Sprague-Dawley rats were used. Recombinant murine or human interleukin-4 was applied topically to the open wounds at doses of 0.1, 1.0, or 10.0 microg/cm(2)/wound for 5 or 10 days. Incisional wounds received the same doses once-at the time of wounding. The time taken to achieve wound closure or wound breaking strength measurements of wounds was recorded and compared with relevant untreated control groups. Wound contraction was impaired in the presence of bacteria, and this was reversed by all doses of recombinant murine interleukin-4. Recombinant murine interleukin-4 had no effect on the wound closure of noncontaminated wounds; it reduced wound breaking strength in acute excisional wounds, except in a contaminated setting when wounds were treated with 1.0 pg/cm(2)/wound. Recombinant interleukin-4 (1.0 microg) improved breaking strength of both diabetic and normal incisional wounds. The apparent pleiotropic effect of interleukin-4 on wound breaking strength under different wound conditions may be related not only to the activity of the fibroblast but also the ratio of cross-linked collagen/total collagen content of wounds. This study suggests that interleukin-4 may be a useful agent for accelerating closure of wounds, particularly where healing is impaired.