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Biomedical subjects

R E Barrow

Publications and source records attributed to R E Barrow.

At least 37 records · Page 2Linked to original sources
PubMed2000

Recombinant human growth hormone treatment in pediatric burn patients and its role during the hepatic acute phase response.

OBJECTIVE: Recombinant human growth hormone (rHGH) has been shown to increase mortality in adult trauma patients; however, little has been reported on its side effects in children. The acute phase response has been suggested to be a contributing factor to trauma mortality. Therefore, the purpose of this study was to examine the effects of exogenous rHGH on the acute phase response in pediatric bum patients. DESIGN: Prospective, randomized, double-blind study. SETTING: Shriners Hospital for Children. PATIENTS: Thermally injured pediatric patients, ranging in age from 0.1 to 16 yrs. INTERVENTIONS: Twenty-eight thermally injured children received either 0.2 mg/kg/day of rHGH or saline (placebo) within 3 days of admission and for at least 25 days. MEASUREMENTS AND MAIN RESULTS: Measurements were patient demographics, incidence of sepsis, inhalation injury, mortality, serum constitutive proteins, acute phase proteins, proinflammatory cytokines and insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3. No differences could be demonstrated in age, gender, burn size, incidence in sepsis (20% vs. 26%), inhalation injury (46% vs. 27%), or mortality (8% vs. 7%) between those receiving rHGH or placebo. Serum IGF-I and IGFBP-3 increased with rHGH treatment, whereas serum IGFBP-1 decreased compared with placebo (p < .05). Burned children treated with rHGH required significantly less albumin substitution to maintain normal levels compared with placebo (p < .05). Those receiving rHGH demonstrated a decrease in serum C-reactive protein and serum amyloid-A and an increase in serum retinol-binding protein compared with placebo (p < .05). rHGH decreased serum tumor necrosis factor-alpha and interleukin (IL)-1beta, whereas no changes were found for serum IL-1alpha, IL-6, and IL-10 compared with placebo (p < .05). Free fatty acids were elevated in burned children who received rHGH (p < .05). CONCLUSION: Data indicate that rHGH does not increase mortality. rHGH decreased acute phase proteins, tumor necrosis factor-alpha, and IL-1beta, which is associated with increases in constitutive hepatic proteins and IGF-I.

Acute-Phase Proteins↗
PubMed2000

Early release of third-degree eyelid burns prevents eye injury.

Burns to the eyelids occur in more than 20 percent of flame injuries and can lead to ocular damage and even blindness. Burn wound contracture can cause ectropion of the eyelid, resulting in exposure keratitis, corneal ulcers, and conjunctivitis. At our hospital, early eyelid release and grafting has made a significant difference in the long-term outcomes of third-degree eyelid burns; however, the question of just how early eyelid release and grafting should take place is an unresolved issue. Fifty-seven children with third-degree eyelid burns were reviewed; 17 had eyelid release within 7 days of receiving eyelid burns and 40 had a delay in eyelid release of more than 7 days after injury. Analysis was by chi-square with the Yates continuity correction or Fisher's exact test when appropriate. Corneal ulcers developed in 2 of 17 of the early eyelid release of third-degree burns, compared with 25 of 40 delayed releases (p = 0.001), exposure keratitis in 3 of 17 early releases, and 30 of 40 in delayed release (p = 0.000); conjunctivitis was identified in 1 of 17 early releases and 14 of 40 delayed eyelid releases (p = 0.025). Release of eyelid burns within 7 days of injury can prevent the development of exposure keratitis, progressive conjunctivitis, corneal ulceration, and the need for corneal surgery. We suggest that early release and grafting should be the treatment of choice for children and young adults with third-degree burns to the eyelids.

Burns↗
PubMed2000

Biobrane improves wound healing in burned children without increased risk of infection.

A synthetic bilaminar membrane used as a skin substitute (Biobrane) has been shown to decrease pain and hospitalization in superficial second-degree burns. Despite these benefits, it has not been utilized universally, particularly in young children, due to a perceived increase in related infections. We propose that when this synthetic membrane is applied to superficial scald burns <25% of the total body surface area (TBSA), decreased healing times are expected without increased risk of infection. Between 1994-1999, 89 children treated within 48 h after receiving superficial partial thickness scald burns covering 5-25% TBSA with no indication of infection were seen at our hospital. Forty-one were assigned randomly to receive treatment with the skin substitute Biobrane and 48 to receive conservative treatment with topical antimicrobials and dressing changes. Comparisons of treatment were made between groups for length of hospitalization, wound healing times, and infectious complications. Children treated with Biobrane or topical antimicrobials were similar in age, race, sex, %TBSA burned, and location of burn. Those receiving Biobrane had shorter hospitalizations and healing times, which was significant for both infants and toddlers and older children. Treatment groups were not different in the use of systemic antibiotics or readmissions for infectious complications. Biobrane was removed in 5.9% of cases for non-adherence. The application of Biobrane within 48 h of superficial burns provides for shorter hospitalizations and faster healing times in children of all ages without increased risk of infection.

Anti-Infective Agents, Local↗
PubMed2000

Glucose effects on lung surfactant kinetics in conscious pigs.

The primary goal of this study was to investigate the effects of glucose infusion on surfactant phosphatidylcholine (PC) metabolic kinetics in the lungs. A new stable isotope tracer model was used in which [1,2-(13)C(2)]acetate and uniformly labeled [U-(13)C(16)]palmitate were infused in 12 normal overnight-fasted pigs to quantify lung surfactant kinetics with or without glucose infusion (24 mg. kg(-1). min(-1)). With glucose infusion, the rate of surfactant PC incorporation from de novo synthesized palmitate increased from the control value of 2.1 +/- 0.2 to 15.5 +/- 1.9 nmol PC-bound palmitate. h(-1). g wet lung(-1) (P < 0.05), whereas the incorporation rate from plasma preformed palmitate decreased from the control value of 20.9 +/- 1.9 to 11.6 +/- 1.1 nmol palmitate. h(-1). g wet lung(-1) (P < 0.05). The palmitate composition in lamellar body surfactant PC increased from the control value of 61.7 +/- 2.1% to 75.9 +/- 0.6% (P < 0.05). The surfactant PC secretion rate decreased from the control value of 239.0 +/- 26.1 to 81.9 +/- 5.3 nmol PC-bound palmitate. h(-1). g wet lung(-1) (P < 0.05). We conclude that, whereas surfactant secretion was inhibited by glucose infusion, neither total surfactant PC synthesis nor the surfactant PC pool size was significantly affected due to an increased reliance on de novo synthesized fatty acids.

Animals↗
PubMed1999

Recombinant human growth hormone alters acute phase reactant proteins, cytokine expression, and liver morphology in burned rats.

BACKGROUND: The effects of exogenous recombinant human growth hormone (rhGH) on hepatic acute phase reactant proteins, cytokine expression, and liver morphology were studied in thermally injured rats to define whether rhGH alters the acute phase response. MATERIALS AND METHODS: Sprague-Dawley rats (56 males) receiving a 60% TBSA third-degree scald burn were randomly divided into two groups to receive either 2.5 mg/kg/day sc rhGH or saline. Rats were sacrificed on Postburn Days 1, 2, 5, and 7. Serum acute phase reactant proteins and cytokines TNF-alpha, IL-1alpha, IL-1beta, and IL-6 were measured. Hepatocyte proliferation, hepatic cytokine gene expression, and liver protein concentrations were determined. RESULTS: Recombinant hGH increased serum albumin on Days 5 and 7 after burn (P < 0.05). Serum haptoglobin and alpha1-acid glycoprotein levels decreased at 2, 5, and 7 days after burn compared to saline (P < 0.05). In rats treated with rhGH, serum IL-1beta decreased 1 day postburn, while serum TNF-alpha increased 5 days after burn compared to saline (P < 0.05). Serum IL-6 and IL-1alpha did not change. Hepatic RNA levels for TNF-alpha were significantly elevated on Day 1 postburn compared to saline (P < 0. 05). Hepatic protein content increased on Days 2, 5, and 7 postburn compared to saline (P < 0.05). Hepatocyte proliferation in rhGH-treated rats increased on Day 5 after burn (P < 0.05). CONCLUSION: Data indicate that rhGH alters the hepatic acute phase response by decreasing type I acute phase proteins and modulating IL-1-like cytokine expression. These changes are associated with increased hepatocyte mitosis and serum and total liver protein concentrations.

Acute-Phase Proteins↗
PubMed1999

Attenuation of the acute-phase response in thermally injured rats by cholesterol-containing cationic liposomes used as a delivery system for gene therapy.

HYPOTHESIS: Cholesterol-containing cationic liposomes alone modulate the acute-phase response and cytokine expression in thermally injured rats and are an effective delivery system for gene therapy in trauma. SETTING: Laboratory. INTERVENTION: Fifty-six adult male Sprague-Dawley rats with a full-thickness scald burn covering 60% of total body surface area were randomly divided into 2 groups to receive either intravenous injections of cholesterol-containing cationic liposomes or saline (control). MAIN OUTCOME MEASURES: Body weights, muscle and liver dry-wet weights, serum levels of constitutive hepatic proteins, acute-phase protein levels, and cytokine levels were determined at 1, 2, 5, and 7 days after thermal injury. RESULTS: Rats receiving cholesterol-containing cationic liposomes had less body weight loss, increased serum transferrin levels, and decreased serum alpha1-acid glycoprotein levels when compared with controls (P<.05). Serum interleukin 1beta and tumor necrosis factor alpha levels were decreased in rats receiving liposomes at 1 and 2 days after burn compared with controls (P<.05). CONCLUSIONS: These results suggest that cholesterol-containing cationic liposomes alone may have a beneficial effect in modulating the hypermetabolic response after burn injury by decreasing type 1 acute-phase proteins and the expression of the proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha. Therefore, cholesterol-containing cationic liposomes appear to be suitable as a delivery system for gene therapy in trauma.

Acute-Phase Reaction↗
PubMed1999

Effect of multiple gene transfers of insulinlike growth factor I complementary DNA gene constructs in rats after thermal injury.

HYPOTHESIS: Multiple subcutaneous injections of cholesterol-containing cationic liposomes encapsulating the complementary DNA (cDNA) gene for insulinlike growth factor I (IGF-I) increase the rate of transfected skin cells and result in increased IGF-I protein levels in the skin with subsequent improvement in wound healing when compared with a single injection. SETTING: Laboratory. INTERVENTION: Twenty-four adult male Sprague-Dawley rats (350-375 g) received a full-thickness scald burn on 60% of their body surface. These rats were randomly divided to receive either 1 injection of liposomes containing 2.2 microg-cytomegalovirus-driven cDNA coding for IGF-I and 0.2 microg of the Lac Z gene cDNA construct, or 2 injections of liposomes containing 2.2 microg cytomegalovirus-driven cDNA coding for IGF-I and 0.2 microg of the Lac Z gene cDNA construct. MAIN OUTCOME MEASURES: Transfection rates and IGF-I protein levels in the skin and physiological responses to the IGF-I gene therapy, evaluated from changes in body weight, protein content in serum and liver, and the rate of burn wound healing. RESULTS: There was a significant decrease in transfection rate and IGF-I protein expression distal from the injection site in animals receiving 1 injection, as compared with a consistent increase in rats receiving multiple injections. Multiple injections improved the response to thermal trauma by increasing the extent of the healed burn wound 33 days after thermal injury (single injection, 31% +/- 1% vs multiple injections, 38% +/- 2%), total serum protein (single injection, 52 +/- 0.5 g/L vs multiple injections, 55 +/- 0.6 g/L), and total liver protein (single injection, 82.0 +/- 0.3 mg/mL vs multiple injections, 91.0 +/- 3.8 mg/mL), P<.05. CONCLUSIONS: Gene transfer rates can be increased by multiple injections of liposomes encapsulating IGF-I cDNA constructs. Increased transfer results in greater IGF-I protein skin concentrations, accelerated wound healing, and increased serum and liver protein concentrations. The clinical relevance of these findings is that liposomal gene constructs should be applied in well-defined distances to improve gene transfer in the skin, and thus clinical outcome after thermal injury.

Animals↗
PubMed1999

Growth hormone attenuates tumor necrosis factor alpha in burned children.

BACKGROUND: Recombinant human growth hormone (rhGH) has been shown to favorably modulate the acute-phase response and may improve the clinical outcome. OBJECTIVE: To examine whether rhGH attenuates the elevated tumor necrosis factor alpha (TNF-alpha) levels that correlate with increased multiorgan failure and mortality in burned adults and children. DESIGN: Twenty children with burns of greater than 40% of the total body surface area were randomly divided into 2 groups to receive placebo (n = 10) or rhGH, 0.2 mg/kg per day intramuscularly (n = 10). SETTING: Pediatric burn hospital. MAIN OUTCOME MEASURE: Serum TNF-alpha levels by enzyme-linked immunoassay at baseline (day 0) and at 21 and 42 days after injury. For statistical analysis, we used the Kruskal-Wallis and Friedman tests. RESULTS: No significant differences in age (mean +/- SD, 6.2+/-1.6 vs 5.0+/-1.2 years) or percentage of total body surface area burn (mean +/- SD, 65.1%+/-8.2% vs 57.1%+/-5.2%) could be shown between the groups given rhGH and placebo. Baseline TNF-alpha levels were elevated from reference values in both groups. Twenty-one and 42 days after rhGH administration, serum TNF-alpha levels were significantly decreased from those at baseline (P<.05). No significant decrease in TNF-alpha levels was observed in the placebo group (P = .5). CONCLUSIONS: Recombinant human growth hormone significantly lowers serum TNF-alpha levels after burn injury. This is consistent with the beneficial effect that rhGH has on the acute-phase response.

Burns↗
PubMed1999

IGF-I gene transfer in thermally injured rats.

Exogenous insulin-like growth factor-I (IGF-I) is known to improve the pathophysiology of a thermal injury, however, deleterious side-effects have limited its utility. Cholesterol-containing cationic liposomes that encapsulate complementary DNA (cDNA) are nonviral carriers used for in vivo gene transfection. We propose that liposome IGF-I gene transfer will accelerate wound healing in burned rats and attenuate deleterious side-effects associated with high levels of IGF-I. To test this hypothesis IGF-I gene constructs, encapsulated in liposomes, were studied for their efficacy in modulating the thermal injury response. Thirty adult male Sprague-Dawley rats were given a 60% TBSA scald burn and randomly divided into three groups to receive weekly subcutaneous injections of liposomes plus the lacZ gene coding for beta-galactosidase, liposomes plus cDNA for IGF-I and beta-galactosidase or liposomes plus the rhIGF-I protein. Body weights and wound healing were measured. Muscle and liver dry/wet weights and IGF-I concentrations in serum, skin and liver were measured by radioimmunoassay. Transfection was confirmed by histochemical staining for beta-galactosidase. Rats receiving the IGF-I cDNA constructs exhibited the most rapid wound re-epithelialization and greatest increase in body weight and gastrocnemius muscle protein content (P < 0.05). Local IGF-I protein concentrations in the skin were higher when compared to liposomes containing only the lacZ gene (P < 0.05) Transfection was apparent in the cytoplasm of myofibroblasts, endothelial cells and macrophages of the granulation tissue. Liposomes containing the IGF-I gene constructs proved effective in preventing muscle protein wasting and preserving total body weight after a severe thermal injury.

Animals↗
PubMed1999

Acute renal dysfunction in severely burned adults.

BACKGROUND: Factors contributing to mortality in burned children with acute renal failure have been identified; however, they have not been identified in thermally injured adults. METHODS: The records of 1,404 acutely burned adults admitted to the Blocker Burn Unit were reviewed. Seventy-six patients with acute renal dysfunction and burns covering more than 30% of their total body surface area with a full-thickness component greater than 10% total body surface area were identified. These patients were divided into those admitted from 1981 through 1989 (n = 35) and those admitted from 1990 to 1998 (n = 41). RESULTS: No significant differences could be shown in the incidence of acute renal dysfunction (5.4 vs. 5.1%) or mortality (88 vs. 87%) for the two time periods, respectively. Sixty-seven percent of the survivors were younger than 40 years of age, compared with only 25% of nonsurvivors (p < 0.02); sepsis was identified in 44 and 96% of survivors and nonsurvivors, respectively (p < 0.001). Fluid resuscitation was delayed in survivors by 1.7+/-1.0 hours compared with 4.4+/-2.1 hours in nonsurvivors (p < 0.001). CONCLUSION: early fluid resuscitation and the prevention of sepsis may reduce the incidence of acute renal dysfunction and mortality in burned adults.

Acute Kidney Injury↗
PubMed1999

Electrical injuries: a 30-year review.

INTRODUCTION: Electrical injuries currently remain a world-wide problem. This study determines whether electrical injuries at our institution have changed in the past 30 years, and identifies electrical burn complications and any high-risk groups. METHODS: From 1967 to 1997, 185 children admitted to our institute were identified with electrical burns. Fifty-five percent of these electrical burns occurred from 1987 to 1997. RESULTS: During the last 10 years of this study, 43% of the electrical injuries (n = 44) were from low voltage (120-240 V) and 57% (n = 58) from high voltage (>1,000 V). In 17 children, serious low-voltage burns were identified as oral commissure burns. These were treated conservatively with one to two reconstructive procedures within 2 years. High-voltage injuries were mainly identified in male children (age 11 to 18 years). Thirty-three percent of high-voltage burns required amputation, 29% had deep muscle involvement, and 24% required either escharotomy or fasciotomy. No mortalities were reported. CONCLUSION: Although the incidence of low-voltage burns is currently on a steady decline, high-voltage injuries remain a problem, particularly in adolescent males.

Adolescent↗
PubMed1999

Lung surfactant kinetics in conscious pigs.

The primary goal of this study was to determine the contributions of plasma free fatty acids (FFA) and de novo synthesized fatty acids (FA) to lung surfactant phosphatidylcholine (PC) synthesis. A new stable isotope tracer model was developed in which [1, 2-(13)C(2)]acetate and uniformly labeled [U-(13)C(16)]palmitate were infused in nine normal overnight fasted pigs to quantify surfactant kinetics in the basal state and during low-dose glucose infusion (2 mg. kg(-1). min(-1)). There was no effect of glucose; therefore, all data were pooled. The surfactant PC-bound palmitate incorporation rate from plasma palmitate was 20.9 +/- 1.9 nmol palmitate. h(-1). g wet lung(-1), compared with the rate of 2.1 +/- 0.3 nmol palmitate. h(-1). g wet lung(-1) from de novo synthesized palmitate. The PC-bound palmitate secretion rate from the lamellar body pool to the alveolar surface pool was 239 +/- 26 nmol palmitate. h(-1). g wet lung(-1). Approximately 90% of the secreted PC recycled back to the lamellar bodies for reutilization. We conclude that plasma is the primary contributor of FA for surfactant PC synthesis under the conditions of this experiment.

Animals↗
PubMed1998

Mortality in burned children with acute renal failure.

BACKGROUND: During the past 13 years, mortality from acute renal failure in burned children has been on the decline. OBJECTIVE: To determine which new burn therapies contributed to the decrease in mortality. DESIGN: The medical records of burned children admitted from February 1966 to January 1997 were reviewed, and the outcome of changes in the treatment of burned children were compared. PATIENTS AND METHODS: Sixty children with acute renal failure were identified. These children were divided into those admitted from 1966 to 1983 (n=24) and those admitted from 1984 to 1997 (n=36). They were compared with matched control subjects from the same period without renal failure. Values are presented as means+/-SEMs. Statistical analysis was by the Student t test or chi2 analysis. RESULTS: Mortality rates in burned children with acute renal failure decreased from 100% before 1983 to 56% after 1984 (P<.001). The time between a burn injury and the initiation of intravenous fluid resuscitation was 8.6+/-1.7 hours before 1983 compared with 3.0+/-0.5 hours after 1984 (P<.005). The time between a burn injury and complete early wound excision decreased from 228+/-37 hours before 1983 to 40+/-7 hours after 1984 (P<.001). The incidence of sepsis decreased from 71% to 44% in these periods (P<.05). After 1984, survivors had a shorter time delay for fluid resuscitation than nonsurvivors (1.7+/-0.5 hours vs 4.8+/-0.9 hours; P<.005) and a lower incidence of sepsis (19% vs 60%; P<.05). From 1984 to 1997, burned children with acute renal failure who did not require dialysis had significantly shorter delays for fluid resuscitation (2.2+/-0.5 hours vs 4.4+/-0.9 hours) and complete wound excision (29+/-6 hours vs 49+/-7 hours) compared with those requiring dialysis (P<.05 for both). CONCLUSION: Early adequate fluid resuscitation, early wound excision, and better infection control may reduce mortality in burned children with acute renal failure.

Acute Kidney Injury↗
PubMed1998

Recombinant human growth hormone modulates Th1 and Th2 cytokine response in burned mice.

OBJECTIVE: To determine whether growth hormone (GH) influences the production of type 1 T-helper (Th1) and type 2 T-helper (Th2) cytokine responses after burn. SUMMARY BACKGROUND DATA: GH has been shown to influence immunoregulation. The authors previously reported improved mortality in burned mice treated with GH after infection with herpesvirus. Other work has shown that impaired immunity after burn was characterized by conversion of Th cell populations from Th1 cells to Th2 cells, suggesting an increased susceptibility of patients with burns to infection. METHODS: The production of Th1 and Th2 cytokine from isolated splenic lymphocytes taken from GH-treated burned mice was measured. RESULTS: At 1 and 11 days after burn, Th1 cytokine production by splenic lymphocytes from burned mice treated with GH was greater than in mice receiving saline. In fact, Th1 cytokine production was greater than that of nonburned mice. In addition, the production of Th2 cytokines was decreased. CONCLUSIONS: Results suggest that the Th1/Th2 response is altered after burn, and this can be reversed with GH. GH, therefore, may improve resistance to infection in patients with burns.

Animals↗
PubMed1998

Growth hormone treatment in pediatric burns: a safe therapeutic approach.

OBJECTIVE: To determine the safety and efficacy of recombinant human growth hormone (rhGH) in the treatment of children who are severely burned. SUMMARY BACKGROUND DATA: During the last decade, we have used recombinant human growth hormone (rhGH; 0.2 mg/kg/day s.q.) to successfully treat 130 children with more than 40% total body surface area (TBSA) burns to enhance wound healing and decrease protein loss. A significant increase in the mortality of adult patients in the intensive care unit who were given rhGH has recently been reported in two large European trials which questions the therapeutic safety of rhGH. METHODS: The records of 263 children who were burned were reviewed. Patients receiving either rhGH at 0.2 mg/kg/day subcutaneously as part of a randomized clinical trial (n = 48) or therapeutically (n = 82) were compared with randomized placebo-administered controls (n = 54), contiguous matched controls (n = 48), and matched patients admitted after August 1997, after which no patients were treated with rhGH (n = 31). Morbidity and mortality, which might be altered by rhGH therapy, were considered with specific attention to organ function or failure, infection, hemodynamics, and calcium, phosphorous, and albumin balance. RESULTS: A 2% mortality was observed in both rhGH and saline placebo groups in the controlled studies, with no differences in septic complications, organ dysfunction, or heart rate pressure product identified. In addition, no difference in mortality could be shown for those given rhGH therapeutically versus their controls. No patient deaths were attributed to rhGH in autopsies reviewed by observers blinded to treatment. Hyperglycemic episodes and exogenous insulin requirements were higher among rhGH recipients, whereas exogenous albumin requirements and the development of hypocalcemia was reduced. CONCLUSIONS: Data indicate that rhGH used in the treatment of children who were severely burned is safe and efficacious.

Adolescent↗
PubMed1998

Effects of insulin on wound healing.

BACKGROUND: Insulin plus glucose, given for 7 days to hypermetabolic burn patients, has been shown to stimulate limb protein anabolism. We hypothesized that insulin plus glucose given to burn patients would also stimulate wound healing. METHODS: Six patients with burns >40% total body surface area were randomized to receive insulin or placebo in a crossover study during the healing of their first and second donor sites. Insulin treatment was titrated at 25 to 49 U/h to achieve a plasma insulin level of 400 to 900 microU/mL for 7 days. Patients receiving insulin received dextrose 50 at 20 to 50 mL/h, titrated to maintain euglycemia. Donor-site biopsies were taken at 7 days and evaluated by three observers blinded to the treatment. RESULTS: The mean (+/-SD) donor-site healing time was reduced from 6.5 +/- 1.0 days with placebo to 4.7 +/- 1.2 days during insulin infusion (p < 0.05). Laminin showed intense staining along the basal lamina and blood vessels. Collagen type IV staining also increased after insulin therapy compared with placebo. CONCLUSION: Data indicate that high doses of insulin and glucose can be safely administered to massively burned patients to improve wound matrix formation.

Adolescent↗
PubMed1998

Growth hormone improves the resistance of thermally injured mice infected with herpes simplex virus type 1.

BACKGROUND: Growth hormone (GH) has been shown to promote wound healing and to improve protein metabolism in burned patients. Through immunomodulation, GH has also protected rats infected with Salmonella typhimurium and mice infected with Escherichia coli. In spite of advances in the management of patient care for those with thermal injuries, high mortality rates of burned patients as a result of infections are of special concern. An improvement in the resistance of burned patients to certain infections will make the beneficial role of GH very clear. In this study, therefore, the immunomodulating effects of recombinant human GH (rhGH) in thermally injured mice exposed to opportunistic herpesvirus infections were investigated. METHODS: (1) Burned mice, exposed to herpes simplex virus type 1 (HSV-1), were treated subcutaneously with rhGH (4 mg/kg) and observed for 21 days to determine the protective antiviral effect of rhGH. (2) Because of reports describing a lack of interferon-gamma (IFN-gamma) responsiveness in burned mice, the IFN-gamma-producing ability of the splenic mononuclear cells (SMNC) from burned mice treated with rhGH was examined. (3) Because the generation of burn-associated suppressor macrophages that can inhibit the IFN-gamma production by SMNC has been previously described, the suppressor cell activities of macrophages from burned mice treated with rhGH were examined. RESULTS: After exposure to lethal amounts of HSV-1, mice treated with rhGH displayed a reduced mortality rate compared with control mice treated with saline. SMNC from burned mice treated with rhGH produced IFN-gamma, whereas this cytokine was not produced by SMNC from burned mice treated with saline. Also, an inhibition of the generation of burn-associated suppressor macrophages was displayed in burned mice treated with rhGH. CONCLUSION: Exogenous administration of rhGH caused an improvement in the resistance of burned mice to HSV-1 infection. In burned mice treated with rhGH, the impaired IFN-gamma responsiveness was restored and the generation of burn-associated suppressor macrophages was inhibited. IFN-gamma, a typical antiviral cytokine induced by rhGH through the regulation of the suppressor macrophage generation, may therefore play a role in the protection of burned mice infected with a lethal amount of HSV-1.

Adjuvants, Immunologic↗