The effect of interleukin-2 administration on wound healing in adriamycin-treated rats.
Adriamycin (doxorubicin hydrochloride), an effective chemotherapeutic drug, is also a potent inhibitor of wound healing. Conversely, certain polypeptide growth factors are capable of stimulating fibroblasts to secrete collagen, thus enhancing wound healing. The purpose of this study was to determine if interleukin-2 (IL-2), a T-cell growth factor, could reverse the wound healing deficit caused by Adriamycin. Adriamycin treatment caused a significant decrease in wound-breaking strength (P less than 0.005). IL-2 administration increased wound-breaking strength in Adriamycin-treated animals (2126 g vs 1549 g, P less than 0.005). In control animals, IL-2 did not increase wound-breaking strength significantly (2708 g vs 2608 g, P greater than 0.1). Histologically, wounds from Adriamycin-treated animals were less cellular, demonstrated less collagen in the dermis, and a lesser degree of capillary ingrowth. The number of fibroblasts in the dermal layer was increased in animals receiving IL-2. Control rats gained an average of 1.4% of their original body weight, while Adriamycin-treated rats lost an average of 19% of their original body weight (P less than 0.0005). IL-2 administration did not influence weight loss or gain. Hematologically, animals receiving Adriamycin had lower hemoglobin and hematocrit values and higher platelet counts. There were no differences in total white blood cell counts; however, animals receiving Adriamycin showed a predominance of polymorphonuclear leukocytes and a relative decrease in lymphocytes. Animals receiving IL-2 demonstrated a significant eosinophilia. (1) Adriamycin impairs normal wound healing. (2) Interleukin-2 administration improves the wound healing impairment caused by Adriamycin. (3) Interleukin-2 appears to increase infiltration of inflammatory cells, fibroblasts, and capillaries into the wound, which may account for the observed increase in wound breaking strength.
DeCunzo
L P
LP
Department of Surgery, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901.
Mackenzie
J W
JW
Marafino
B J
BJ
Devereux
D F
DF
D000818:Animals; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013601:T-Lymphocytes / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
D007376:Interleukin-2; D004317:Doxorubicin; D003094:Collagen