Temporal expression of cytokines in rat cutaneous, fascial, and intestinal wounds: a comparative study

Previous studies have shown that healing in intestinal wounds is proportionally faster than skin. Cytokines and growth factors play a major role in these coordinated wound-healing events. We hypothesized that this more rapid intestinal healing is due to an early upregulation of proinflammatory cytokines (IL-1beta, TNF-alpha, and IFN-gamma), followed by increases in the expression of the anti-inflammatory cytokine IL-10 and growth factor TGF-beta.

Four wounds (skin, fascia, small intestinal, and colonic anastomosis) were created in each of 48 juvenile male Sprague Dawley rats; tissue samples of each site were harvested at 0, 1, 3, 5, 7, and 14 days postoperatively (n = 8/group) and levels of IL-1beta, IFN-gamma, TNF-alpha, IL-10 and TGF-beta expression from each site were measured using ELISA kits.

IL-1beta expression peaked earlier in small-intestinal and colonic wounds when compared to skin or fascia (e.g., small intestine: day 3 and colon day 5, P < 0.05 by ANOVA). Post-wounding levels of TNF-alpha were elevated in fascial wounds, but decreased in small-intestinal and colonic wounds. IFN-gamma levels were not significantly altered in any wounds. IL-10 showed a similar downregulation pattern in all wounds, while TGF-B levels were decreased in colonic and fascial wounds, but relatively unchanged in SI and skin.

An earlier peak in IL-1beta levels and a consistent decrease in TNF-alpha were seen in healing intestinal tissues; but no clear pattern of increased anti-inflammatory or regulatory cytokines was seen, which might explain the earlier healing of intestinal tissues. Additional studies are required to determine the role of individual cytokines, or the intrinsic reactivity of the tissues may explain the site specific differences of healing rates in different tissues.