Stress to the body, such as trauma with fracture or haemorrhage, burn injury or major elective surgical procedures, leads to alterations in immune functions and an attenuated immune response (Faist et al., 1986). This predisposes to the development of infectious complications in the days or weeks following injury. It is estimated that, among patients who die more than 24 h after hospitalization following trauma, 75% die as a result of complications of infection and the inflammatory response (Miller et al., 1982). It is in limiting this immune dysfunction that supplemental dietary arginine appears to hold most promise (see Evoy et al., 1998).
Barbul and co-workers demonstrated that supplemental dietary arginine reduced trauma-induced thymic involution, lessened weight loss, improved wound healing and prolonged survival in injured rats (see Barbul, 1977). The same group also demonstrated that a dietary supplement of 1% arginine by weight increased thymic weight and the number of thymic lymphocytes in normal healthy mice and rats (see Barbul, 1986, 1996). In a burn model in guinea pigs, Saito et al. (1987) showed an increase in delayed hypersensitivity and in survival in arginine-supplemented animals. Madden et al. (1988) demonstrated a similar survival advantage in animals subjected to lethal bacterial peritonitis. This finding was replicated by Gianotti et al. (1993), who, in addition to improved survival, found a reduction in bacterial translocation and increased bactericidal activity in the arginine-supplemented animals.
The anti-tumour activity of arginine has been studied in a number of models, with variable results. In the setting of protein-calorie malnutrition and tumour inoculation, supplemental arginine (1% by weight) reduced the growth rate of the immunogenic neuroblastoma C1300 and improved host survival compared with glycine-supplemented controls (Fig. 5.4), while a similar effect was not seen in mice bearing a poorly immunogenic neuroblastoma TBJ (Reynolds et al., 1990). Similar differences have been seen in different models of breast and colon cancer. The impression is of a dual effect of arginine: improving host resistance while simultaneously improving tumour-cell survival, the end result depending on the balance between these two opposing actions. The potential benefit of arginine supplementation in cancer therapy was further highlighted in a study by Lieberman et al. (1992), in which mice bearing the C1300 neuroblastoma were treated with a combination of arginine and IL-2: combined therapy led to a reduction in tumour growth and prolonged host survival, compared with the control group or either treatment alone.
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