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Inhibition of wound repair by thymichormonesAdrian Barbul, MD, FACS, Toby Shawe, MD, Heidi L. Frankel, MD,Jonathan E. Efron, BA, and Hannah L. Wasserkrug, BA, Baltimore, ¡\id.

To further define the Tole of the thymus in wound healing, we studied the effects of twothymic hormones on fibroplasia in normal euthymic and in nude athymic mice. Groupsof 10 mice underwent a 2.5 cm dorsal skin incision with subcutaneous placement ofpolyvinyl alcohol sponges. Starting on the day of wounding, the following dailyin jections were given: (1) thymopentin (TP5), an active synthetic pentapeptide ofthymopoietin, a naturally occurring thymic hormone (1 p.g/day/IM),. (2) thymulin orfacteur thymique serique (FTS), a naturally occurring circulating thymic hormone(0.2 JJ.g/day/IM); (3) control saline solution (0.1 ml/day/I¡W). All mice were killed 4weeks after wounding, and wound breaking strength and hydroxyproline content of thesponge granulomas were measured. The results show that both thymic hormonesimpaired wound breaking strength and reparative collagen synthesis in normal andathymic m ice. The magnitude of the wound healing impairment induced by the twohormones was equal in the thymus-bearing and in the nude mice. The data supp6rtprevious findings, which suggested that the thymus has an inhibitory effect on wound

healing. (SUR(;ERY 1989;106:373-7.)

From the Departments 01 Surgery, Sinai Hospital and The Johns HoPkins Medicallnstitutions, Baltimore, Md.

THE COMPLEX BIOCHEMICAL and cellular events thatcompose the cascade of wound healing have been rec-ognized as being under the regulation of the immunesystem. The cellular arm of the irnmune system, com-posed mainly of macrophages and lymphocytes, plays amajor role in influencing wound repair. Wound mac-rophages, which are known to be key elements in woundhealing, can influence endothelial cell and fibroblast ac-tivity via secreted monokines.l Wound T lymphocytesalgo play an important role in wound healing. Resultsof in vitro studies have shown that lymphokines, secre-tory products of activated lymphocytes, can exert bothpositive and negative effects on fibroblast migration,replication, and collagen synthesis.2 In vivo depletion ofT lymphocytes results in impaired wound healing, asassessed by wound breaking strength and collagendeposition.3 T lymphocytes mature and acquire func-

tional characteristics in the thymus. The role of the thy-mus on fibroplasia, however, is not clear. We have pre-viously shown that thymectomy in adult animals re-sulted in increased wound maturation; this effect wasabrogated by intraperitoneal implantation of Milliporechambers containing thymic fragments, suggesting thatthe thymus exerts an inhibitory effect on normal woundhealing.4 To delineate more clearly the role of the thy-mus in fibroplasia, we studied the effect of thymic hor-manes on wound h"<;aling in normal and athymic mice.

MATERIAL AND METHODS

Thirty male BALB / c mice and 30 male athymic nudemice (nu/nu, originally of BALB/c background) werepurchased from Harlan Sprague-Dawley Inc. (India-napolis, Ind.) at the age of 7 weeks. Groups of five an-imals were housed in clear plastic shoe box-type cages.The cages of the nude mice were sterilized and coveredwith protective barriers. The thymus-bearing BALB/cmice received a standard laboratory chow (TekladMouse/Rat 5010 Autoclavable Diet, Harlan Sprague-Dawley) and tap water ad libitum. Nude mice were of-fered the same diet, which had been previously auto-claved, and drank sterile acidified water (pH 2.5). AIlmice were allowed at least 1 week of acclimatization to

Presented at the Fiftieth Annual Meeting of the Society ofUniversity Surgeons, Baltimore, Md., Feb. 9-11,1989.

Supported by National lnstitutes of Health grant 1 R29GM38650.Reprint requests: A. Barbul, MD, Department of Surgery,Sinai Hospital, 2401 W. Belvedere Ave., Baltimore, MD21215.

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SURGERY 373