Topical glutamine therapy in experimental inflammatory bowel disease.

This study investigated the effects of glutamine and steroid enemas on disease activity in an animal model of colitis. Colitis was induced in male Wistar rats by intracolonic instillation of 30 mg trinitrobenzenesulphonic acid in 50% ethanol (TNBS/E). Controls were given an isovolumetric bolus of normal saline. After 24 h, animals were randomised to receive enemas (1 mL twice daily) of prednisolone (200 mg/L), or L-glutamine (500 g/L) or the suspending agent (placebo). On day 8, the colon was weighed and the degree of inflammation assessed using a colon macroscopic score (CMS). Thymic weight, splenic weight, percentage gain in body weight (%GBW), food intake, plasma interleukin-6 (IL6) and plasma alpha(2)-macroglobulin (alpha(2)M) were also determined. There was a significant increase in CMS, colon weight, splenic weight, IL6 and alpha(2)M in TNBS/E animals compared to controls (P< 0.01). There was also a significant decrease in %GBW, food intake and thymic weight in TNBS/E animals (P< 0.01). The therapeutic enema of prednisolone reduced colonic inflammation (CMS, colon weight), improved thymic weight, %GBW and food intake, and reduced plasma IL6 concentrations (P< 0.05). In contrast administration of glutamine enemas was associated with an exaggerated acute phase protein (alpha(2)M) response (P< 0.05) and failed to improve the colonic and systemic inflammatory response in this experimental model of colitis.

Manipulation of the L-arginine-nitric oxide pathway in experimental colitis.

The role of the L-arginine-nitric oxide pathway in the pathogenesis of colonic inflammation was assessed using L-arginine and its competitive analogue N omega-nitro-L-arginine methyl ester (L-NAME) in a rat model of colitis. In the first study oral L-arginine 2 per cent (control: 3.4 per cent L-glycine) was administered with and without L-NAME 100 mg/l. Orally administered L-arginine increased colonic inflammation (P = 0.004) and decreased thymic weight (P = 0.0007). Addition of L-NAME reduced the colonic inflammation and prevented loss of body-weight (P < 0.04). In the second study L-NAME was administered orally in concentrations of 100, 200 and 500 mg/l (control: no L-NAME). L-NAME 500 mg/l reduced colonic inflammation and increased thymic weight and body-weight (P < 0.01). Thymic weight and body-weight correlated positively with the concentration of L-NAME administered orally (rs > or = 0.3, P = 0.04). L-NAME l g/l was administered topically as an enema (control: suspension agent). Topical L-NAME reduced colonic inflammation and increased thymic weight (P < 0.05). These results suggest that the L-arginine-nitric oxide pathway mediates colonic inflammation in this model.

Metabolic effects of arginine in a healthy elderly population.

Recently there has been much interest in the use of arginine to stimulate immune responses and to promote wound healing. In the present study, the effect of an oral supplementation with arginine on the metabolism of 45 healthy, nonsmoking, elderly volunteers was investigated. Subjects were divided into two groups that received either arginine aspartate (17 g free arginine) (n = 30) or a placebo (n = 15). The supplements were taken for a period of 14 days. Dietary intake of food was not controlled. Blood chemistry, lipid profiles, and as an index of nutritional status, serum insulin-like growth factor-1 levels and nitrogen balance were compared before and after supplementation. Two weeks of arginine supplementation led to a significant elevation of serum insulin-like growth factor concentrations and an improved and positive nitrogen balance (2.0 +/- 0.41 g N) when compared with controls (0.11 +/- 0.47 g N; p = 0.0114). In addition the arginine-supplemented group demonstrated a decreased total serum cholesterol with a reduction in the low-density lipoprotein but not the high-density lipoprotein fraction resulting in a increase in the ratio of low- to high-density lipoprotein fraction. No adverse effects were observed at this dosage of arginine. The data suggest that oral arginine supplementation may be used safely in elderly humans.

Modulation of immune function and weight loss by L-arginine in obstructive jaundice in the rat.

Jaundiced surgical patients have a high incidence of postoperative complications. Many causative factors have been identified including cachexia and immune suppression. The amino acid L-arginine has anabolic and immunostimulatory properties. It was hypothesized that dietary supplementation with L-arginine would diminish the weight loss and immune suppression of obstructive jaundice. Sixteen male Wistar rats rendered jaundiced by bile duct ligation were allocated to two groups. The test group (n = 8) received drinking water supplemented with 1.8 percent L-arginine ad libitum and the control group (n = 8) received a solution of isonitrogenous glycine. Both groups had free access to standard chow. Body-weight, and fluid and food intake were recorded. After 21 days, delayed-type hypersensitivity to 2,4-dinitrofluorobenzene was assessed. Animals receiving L-arginine consumed more food than controls (mean(s.e.m.) 414(16) versus 360(13) g, P < 0.05) and lost less weight (mean(s.e.m.) proportion of initial body-weight lost 7.8(1.2) versus 14.8(1.4) percent, P < 0.05). The delayed-type hypersensitivity response was significantly greater in rats receiving L-arginine (mean(s.e.m.) increase in ear thickness 23.9(2.7) versus 9.4(2.1) percent, P < 0.05). In this animal model of obstructive jaundice dietary supplementation with L-arginine diminished both weight loss and immune suppression.

Arginine stimulates wound healing and immune function in elderly human beings.

BACKGROUND: Experimentally, arginine enhances immune function and promotes wound healing. In this randomized double-blind study we investigated the effect of oral arginine supplementation on wound healing and T-cell function in elderly human beings (more than 65 years of age). METHODS: Thirty elderly, healthy, human volunteers (15 men and 15 women) received daily supplements of 30 gm arginine aspartate (17 gm free arginine). Fifteen volunteers (nine men and six women) received a placebo syrup. Fibroplastic wound responses were assessed by inserting a polytetrafluoroethylene catheter subcutaneously into the right deltoid region. Epithelialization was examined by creating a 2 x 2 cm split thickness wound on the lateral aspect of the upper thigh. Mitogenic response of peripheral blood lymphocytes to concanavalin A, phytohemagglutinin, pokeweed mitogen, and allogeneic stimuli was assayed at the beginning and end of supplementation. Polytetrafluoroethylene catheters were analyzed for alpha-amino nitrogen (assessment of total protein accumulation), hydroxyproline (index of reparative collagen synthesis), and DNA accumulation (index of cellular infiltration). RESULTS: Arginine supplementation for 2 weeks significantly enhanced wound catheter hydroxyproline accumulation (26.49 +/- 2.39 nmol/cm vs 17.41 +/- 2.04 nmol/cm) and total protein content (43.47 +/- 3.85 micrograms/cm vs 21.95 +/- 2.5 micrograms/cm). Arginine did not influence the DNA content of the catheters or the rate of epithelialization of the skin defect. Peripheral blood lymphocyte responses to mitogenic and allogenic stimulation were greater in the arginine supplemented group. Serum insulin-like growth factor-1 levels were significantly elevated in the arginine group. CONCLUSIONS: The data suggest that arginine supplementation may improve wound healing and immune responses in the elderly.

Arginine enhances T-cell responses in athymic nude mice.

Supplemental L-arginine has been shown to enhance thymic and T-cell responses in rodents. We examined the ability of supplemental dietary L-arginine to induce T-cell function in athymic nude mice that lack a normally developed T-cell system. Groups of male nude (nu/nu) mice (Balb/c background) 7 to 8 weeks old were given for 2 weeks 1.2% arginine hydrochloride solution for drinking, whereas controls received acidified tap water. All mice ingested a standard laboratory chow. In the first experiment, the arginine-supplemented animals had significantly greater number of T cells in the spleen (assessed by the number of Thy 1.2-positive lymphocytes) and these cells had enhanced mitogenic responses to mitogenic stimulation (phytohemagglutinin and concanavalin A). In vivo delayed-type hypersensitivity responses to 2,4-dinitro-1-difluorobenzene were also significantly increased after the 2 weeks of arginine supplementation. In a second experiment, mice maintained under the same conditions were skin grafted with rat tail skin. Animals were observed for 100 days for rejection but no significant difference was noted in skin graft survival. We conclude that dietary arginine can increase extrathymic T-cell maturation and function, but cannot induce in vivo allogeneic graft recognition in athymic nude mice.