Cutaneous barrier repair and pathophysiology following barrier disruption in IL-1 and TNF type I receptor deficient mice

Disruption of the permeability barrier elicits a homeostatic repair respons e which rapidly restores barrier function while repeated barrier perturbati on results in cutaneous pathology. In response to barrier disruption there is a marked increase in epidermal TNF-alpha and IL-1 production. To determi ne the potential role of TNF and IL-1 in mediating the cutaneous changes th at occur following barrier disruption we compared the kinetics of barrier r ecovery and the degree of epidermal hyperplasia and cutaneous inflammation in TNF type I(p55) receptor and IL-1 receptor type I(p80) deficient mice. N o abnormalities in epidermal morphology were observed with light or electro n microscopy in receptor deficient mice. Under baseline conditions epiderma l barrier function was unchanged in receptor deficient mice. Following barr ier disruption the kinetics of barrier recovery were similar in control vs TNF receptor deficient mice regardless if the barrier was disrupted by acet one treatment, SDS treatment, or tape stripping. In contrast, barrier recov ery was slightly but significantly accelerated regardless of the method of barrier disruption in IL-1 receptor deficient mice. The degree of epidermal hyperplasia and cutaneous inflammation following repeated barrier disrupti on was similar in control, TNF receptor, and IL-1 receptor deficient mice. The present study demonstrates that barrier recovery is not delayed and the degree of epidermal hyperplasia and inflammation are not altered in either TNF receptor or IL-1 receptor deficient mice, indicating that neither TNF nor IL-1 alone are essential for either barrier repair or the cutaneous pat hology induced by barrier perturbation. Whereas the increase in IL-1 follow ing barrier disruption may delay components of the repair response, whether either TNF-alpha or IL-1 regulate aspects of the homeostatic response rema ins unresolved.