leptin and Wounds-and-Injuries

Both overnutrition and undernutrition affect energy metabolism, with overnutrition raising energy expenditure and undernutrition lowering it. Fever is a powerful stimulator of thermogenesis. In diseases such as cancer, AIDS, diabetes mellitus, and rheumatoid arthritis, whether energy expenditure is increased or decreased often depends on how advanced the disorder is. Early on, when the greater protein turnover characteristic of these conditions is paramount, energy expenditure is increased. In addition, in diseases such as cancer, AIDS, and rheumatoid arthritis in which cytokines are released, the cytokines' thermogenic effect initially increases the metabolic rate. However, as the disease becomes more advanced and leads to cachexia, energy expenditure drops below normal. Acute conditions such as burns and trauma significantly raise energy expenditure, primarily by increasing sympathetic response and the release of catecholamines, which are powerful stimulators of energy expenditure.

Topics: Acquired Immunodeficiency Syndrome; Adult; Age Factors; Aged; Arthritis, Rheumatoid; Basal Metabolism; Burns; Diabetes Mellitus; Eating; Energy Metabolism; Female; Humans; Leptin; Male; Middle Aged; Neoplasms; Obesity; Wounds and Injuries

Leptin is thought to play an important role in the regulation of the immune system. In patients, leptin is inversely proportional to interleukin-6 (IL-6) levels. Thus, the objective of our study was to evaluate a dose-dependent therapeutic impact of leptin with possible IL-6-dependency on immune actions and outcome in a trauma/sepsis model.. Sixty-nine wild-type and 63 IL-6 mice were subdivided into three groups: trauma/sepsis group (first hit: femur fracture and hemorrhage; second hit: cecal ligation and puncture 2 days later), trauma group (first hit and laparotomy), sham group (laparotomy only). Each group received vehicle or leptin (2.5 μg/g (leptin1) or 5 μg/g (leptin2)) subcutaneously and was observed for 8 days after induction of the first hit. Mortality, humoral, and cellular immune markers were determined.. We revealed a dose-dependent anti-inflammatory effect of exogenous leptin in the sepsis groups and to some extent a pro-inflammatory effect in the sham groups. Leptin administration resulted in a decreased mortality in septic wild-type mice (trauma/sepsis vehicle group: 36.4%, trauma/sepsis leptin1 group: 25%, trauma/sepsis leptin2 group: 0%) and in an increased mortality in septic IL-6 mice (53.8%, 83.4%, 100%). All mice of the trauma groups and sham groups survived. In wild-type trauma/sepsis mice, exogenous leptin led to increased levels of CD4 and CD8 in the spleen, and a less pronounced type IV hypersensitivity (P ≤ 0.039). Furthermore, it decreased the levels of tumor necrosis factor-α and IL-6, not reaching statistical significance.. Due to the fact that leptin administration to traumatized and septic mice seems to have a positive effect on their outcome via IL-6 and does not negatively impact their medical condition if applied preventively, leptin might be a therapeutic agent for the prevention, or treatment of sepsis-related detrimental outcome after initial trauma.

Topics: Animals; Anti-Inflammatory Agents; Immunity, Cellular; Immunity, Humoral; Interleukin-6; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Sepsis; Wounds and Injuries

Hydrocellular foam dressing (HCF) absorbs excessive wound fluid, which contains various cytokines and growth factors, and ensures a moist environment to promote wound healing. However, the molecular mechanisms underlying the wound fluid component changes induced by HCF are poorly understood. In the present study, we examined the effect of HCF on wound healing and the associated regulatory mechanisms in relation to variations in cytokine levels in the wound fluid. We created full-thickness wounds on the dorsolateral skin of rats and collected the resulting wound fluid samples. HCF was immersed in a plate containing the wound fluids. HCF was then removed and the excess wound fluid remaining in the plate was examined by cytokine array and enzyme-linked immunosorbent assay. We also used a rat model and human dermal fibroblast cultures to examine the effect of wound fluid component changes during the wound healing process. Upon treatment with HCF, leptin levels were upregulated in the wound fluid. Fibroblast proliferation was enhanced and the effect was suppressed in the presence of leptin antagonist. In our in vivo model, HCF increased wound contraction compared with film dressings and this positive effect of HCF was suppressed by addition of leptin antagonist. Our results suggest that dermal fibroblast proliferation is upregulated by HCF due to increased leptin level at the wound surface, and these effects promote wound healing. We believe that the present study contributes to furthering the understanding of the mechanisms underlying the effects of HCF-induced wound healing.

Topics: Animals; Bandages, Hydrocolloid; Body Fluids; Cell Proliferation; Cells, Cultured; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Immunoblotting; Leptin; Male; Rats; Rats, Wistar; Skin; Wound Healing; Wounds and Injuries

To investigate the effect of leptin on collagen systhesis in wounded rats.. Thirty male Wistar rats, weight (180 +/- 20)g, were randomly divided into three groups (n = 10) by weight: normal depilation group, wound control group and leptin treatment group and ten rats were included in each group. A full-thickness defect measuring 2 x 2.5 cm was made in the back of rats in wound control group and leptin treatment group. Each wound in rats of leptin treatment group was applied topically with 0.1 ml leptin solution (2.0 microg leptin), daily for 7 days and that of wound control group with equivalent saline solution. All rats were killed and then granulation tissues samples and skin were collected to examine the synthesis of collagen.. Hydroxyproline content in granulation tissues of in leptin treatment group (33.92 +/- 3.09) mg/g were significantly increased than those in control group (29.55 +/- 3.59 mg/g, P < 0.05). The mRNA expressions of collagen I and III were significantly enhanced in leptin treatment group (0.96 +/- 0.09, 0.09 +/- 0.06) than those in control group (0.80 +/- 0.03, 0.08 +/- 0.03). The levels of type I and III collagen were significantly increased in leptin treatment group than those in control group.. Leptin applied topically can accelerate wound healing through enhancing gene expression of type I and III collagen and synthesis of collagen in wound tissue.

Topics: Administration, Cutaneous; Animals; Collagen Type I; Collagen Type III; Leptin; Male; Rats; Rats, Wistar; RNA, Messenger; Wound Healing; Wounds and Injuries

Motor vehicle accidents (MVA) represent a complex physical and emotional stressor. Consequent short- and/or long-term alterations on the circulating concentrations of stress hormones and adipo-cytokines may have potential health implications. Fifty-nine children and adolescents, aged 7-18 years, were evaluated within 24 h after hospitalization for a MVA, and 1 and 6 months later; 40 children served as controls. We examined longitudinally the effects of physical injury-associated (PI) group vs. emotional-only stress (ES) group on circulating cortisol, catecholamine, interleukin (IL)-6, leptin and adiponectin concentrations. Within 24 h after the accident, serum cortisol concentration was greater than the controls in the PI but not the ES group (p = 0.02), while serum IL-6 concentration was greater in both trauma groups than in the controls (p = 0.004 for PI, p = 0.04 for ES). Adiponectin concentration was lower in the PI than the ES (p = 0.031) and the control (p = 0.019) groups and this was mainly attributed to females. The catecholamine and leptin concentrations were similar in the three groups. At the 1 and 6 month evaluations, cortisol and IL-6 concentrations in both trauma groups became normal. Adiponectin concentration in females, however, remained low 1 and 6 months after the accident (p = 0.03 for month six). In conclusion, circulating IL-6 concentration was influenced equally by the physical and emotional stress shortly after the trauma. Physical but not emotional-only stress lowered the circulating adiponectin concentrations in females and this effect persisted for at least 6 months.

Topics: Accidents, Traffic; Adiponectin; Adolescent; Catecholamines; Child; Female; Humans; Hydrocortisone; Interleukin-6; Leptin; Male; Sex Factors; Stress, Psychological; Wounds and Injuries

This study focused on the regulation of prostaglandin (PG) production in diabetes-impaired wound tissue. Cyclooxygenase (COX)-1 and -2 expression and activity were severely dysregulated in chronic wounds of diabetic ob/ob mice. Those wounds were characterized by a reduced expression of COX-1 and the presence of strongly elevated levels of COX-2 when compared with conditions observed in healthy animals. Resolution of the diabetic and impaired wound-healing phenotype by systemic administration of leptin into ob/ob mice increased COX-1 expression in wound margin keratinocytes and decreased COX-2 expression in inner wound areas to levels found in wild-type animals. Notably, improved wound healing was characterized by a marked increase in PGE2/PGD2 biosynthesis that colocalized with induced COX-1 in new tissue at the margin of the wound. COX-2 expression did not significantly contribute to PGE2/PGD2 production in impaired wound tissue. Accordingly, only late wound tissue from SC-560-treated (selective COX-1 inhibitor) but not celecoxib-treated (selective COX-2 inhibitor) ob/ob mice exhibited a severe loss in PGE2, PGD2, and prostacyclin at the wound site, and this change was associated with reduced keratinocyte numbers in the neo-epithelia. These data constitute strong evidence that a dysregulation of COX-1-coupled prostaglandin contributes to diabetes-impaired wound healing.

Topics: Animals; Cyclooxygenase 1; Cyclooxygenase 2; Diabetes Mellitus, Type 2; Dinoprostone; Disease Models, Animal; Inflammation; Leptin; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Recombinant Proteins; Wound Healing; Wounds and Injuries

The effects of recombinant human erythropoietin (rHuEPO) in diabetes-related healing defects were investigated by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ-m(+/+)Lept(db) mice (db(+)/db(+)) and their normoglycemic littermates (db(+/+)m). Animals were treated with rHuEPO (400 units/kg in 100 microl s.c.) or its vehicle alone (100 microl). Mice were killed on different days (3, 6, and 12 days after skin injury) for measurement of vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, for monitoring angiogenesis by CD31 expression, and for evaluating histological changes. Furthermore, we evaluated wound-breaking strength at day 12. At day 6, rHuEPO injection in diabetic mice resulted in an increase in VEGF mRNA expression (vehicle = 0.33 +/- 0.1 relative amount of mRNA; rHuEPO = 0.9 +/- 0.09 relative amount of mRNA; P < 0.05) and protein wound content (vehicle = 23 +/- 5 pg/wound; rHuEPO = 92 +/- 12 pg/wound; P < 0.05) and caused a marked increase in CD31 gene expression (vehicle = 0.18 +/- 0.05 relative amount of mRNA; rHuEPO = 0.98 +/- 0.21 relative amount of mRNA; P < 0.05) and protein synthesis. Furthermore, rHuEPO injection improved the impaired wound healing and, at day 12, increased the wound-breaking strength in diabetic mice (vehicle = 12 +/- 2 g/mm; rHuEPO 21 +/- 5 g/mm; P < 0.05). Erythropoietin may have a potential application in diabetes-related wound disorders.

Topics: Animals; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Erythrocyte Count; Erythropoietin; Female; Glycated Hemoglobin; Hemoglobins; Humans; Leptin; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Neovascularization, Physiologic; Platelet Endothelial Cell Adhesion Molecule-1; Recombinant Proteins; RNA, Messenger; Skin; Vascular Endothelial Growth Factor A; Wound Healing; Wounds and Injuries

To assess dynamics of serum leptin concentrations (as a possible marker of stress) at some surgical patients during short perioperative period.. The serum leptin concentrations were estimated in group of patients with trauma or large bowel diseases in stress of both own disease and next elective or urgent surgery. The subgroups of patients were: a) monotrauma (13), b) polytrauma (10), c) malignant (20) or d) inflammatory disease (13) of large bowel. The serum leptin concentrations were evaluated preoperatively and during 16 hours postoperatively-immediately after surgery, after 8 and 16 hours after operation. The serum IL-6 concentrations were estimated immediately and 48 hours postoperatively.. The serum leptin concentrations showed a time depending dynamic phase: they decreased postoperatively and increased during the first 16 hours postoperatively. It was more expressed in the malignant bowel disease subgroup. A correlation between age and serum leptin concentrations was not found in any subgroup. We found correlation between serum leptin concentrations preoperatively and postoperatively.. The serum leptin concentrations demonstrated some dynamics in short perioperative periods. It was very considerably in patients with large bowel malignancy. Any significant difference in serum IL-6 concentrations was not discovered preoperatively and postoperatively in all subgroups.

Topics: Humans; Interleukin-6; Intestinal Diseases; Leptin; Stress, Physiological; Surgical Procedures, Operative; Wounds and Injuries