Abstract

Skin allografts have been successfully used for temporary wound coverage in burn patients receiving conventional immunosuppressive drugs. With this procedure, unprecedented survival has been shown when 90% mortality was expected. Cyclosporine (CyA), a powerful new immunosuppressive agent, could provide a more effective method to enhance skin allograft survival in burn patients. By using CyA and allografted skin, completely healed burn wounds could be obtained in days rather than weeks. To study the feasibility of this concept, we will investigate the following in a rat burn model: 1. CyA's effect on animal survival in combination with a 50% body surface area thermal injury. 2. CyA's effect on the survival of rat skin allografts transplanted across a strong histocompatibility barrier in the rat burn model. 3. The immune responsiveness of thermally injured rats undergoing skin transplantation, CyA therapy, and bacterial challenge (both systemic and topical challenge). 4. Possible toxicity associated with CyA therapy. 5. Simple, efficient, and predictable quantitative methods to monitor the rejection process. Thus, CyA's effectiveness in prolonging skin transplant survival in rats undergoing massive thermal injury will be delineated. In addition, the immune response of rats receiving CyA treatment will be studied in an effort to understand whether CyA totally suppresses the immune response or only selectively suppresses it, thus allowing immune responsiveness against bacterial infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031974-03
Application #
3280434
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1984-01-01
Project End
1986-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697

  Publications

Hewitt, C W; Black, K S; Aguinaldo, A M et al. (1988) Cyclosporine and skin allografts for the treatment of thermal injury. I. Extensive graft survival with low-level long-term administration and prolongation in a rat burn model. Transplantation 45:8-12
Black, K S; Hewitt, C W; Smelser, S et al. (1988) Cyclosporine and skin allografts for the treatment of thermal injury. II. Development of an experimental massive third-degree burn model demonstrating extensive graft survival. Transplantation 45:13-6
Black, K S; Hewitt, C W; Henson, L E et al. (1987) Cyclosporine-induced long-term allograft survival and its potential in posttrauma tissue replacement. J Burn Care Rehabil 8:531-5
Hewitt, C W; Black, K S; Gonzalez, G A et al. (1987) Decreased reactivity of allosera against target lymphocytes obtained following thermal injury or long-term cyclosporine treatment. Clin Immunol Immunopathol 45:395-404
Black, K S; Hewitt, C W; Grisham, G R et al. (1987) Two new composite tissue allograft models in rats to study neuromuscular functional return. Transplant Proc 19:1118-9
Grisham, G R; Black, K S; Hewitt, C W et al. (1987) Prior administration of donor-strain epidermal cells or macrophages to enhance survival of rat hind-limb allografts. Transplantation 44:572-4
Martin, D C; Hewitt, C W; Black, K S et al. (1987) Induction of long-term rat renal allograft survival: a specific synergistic effect of limited pretransplant cyclosporine combined with multiple nonspecific blood transfusions. Transplant Proc 19:462-3
Hewitt, C W; Black, K S; Gonzalez, G A et al. (1987) Long-term residual cyclosporine levels following short-term administration in various allograft models demonstrating extensive survival prolongation. Transplant Proc 19:1244-5
Biren, C A; Barr, R J; McCullough, J L et al. (1986) Prolonged viability of human skin xenografts in rats by cyclosporine. J Invest Dermatol 86:611-4
Achauer, B M; Hewitt, C W; Black, K S et al. (1986) Long-term skin allograft survival after short-term cyclosporin treatment in a patient with massive burns. Lancet 1:14-5

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