leptin and Lymphopenia

Leptin, the product of the ob gene, is a pleiotropic molecule that regulates food intake as well as metabolic and endocrine functions. Leptin also plays a regulatory role in immunity, inflammation, and hematopoiesis. Alterations in immune and inflammatory responses are present in leptin- or leptin-receptor-deficient animals, as well as during starvation and malnutrition, two conditions characterized by low levels of circulating leptin. Both leptin and its receptor share structural and functional similarities with the interleukin-6 family of cytokines. Leptin exerts proliferative and antiapoptotic activities in a variety of cell types, including T lymphocytes, leukemia cells, and hematopoietic progenitors. Leptin also affects cytokine production, the activation of monocytes/macrophages, wound healing, angiogenesis, and hematopoiesis. Moreover, leptin production is acutely increased during infection and inflammation. This review focuses on the role of leptin in the modulation of the innate immune response, inflammation, and hematopoiesis.

Topics: Adaptation, Physiological; Adipose Tissue; Animals; Anorexia; Apoptosis; Cachexia; Carrier Proteins; Cell Division; Cytokines; Eating; Endocrine System; Hematopoiesis; Humans; Immune System; Infections; Inflammation; Interleukin-6; Leptin; Lymphopenia; Mice; Mice, Mutant Strains; Multigene Family; Neovascularization, Physiologic; Obesity; Organ Specificity; Phagocytes; Rats; Receptors, Cell Surface; Receptors, Cytokine; Receptors, Leptin; Signal Transduction; Starvation; T-Lymphocyte Subsets

Neuroendocrine hormones have profound effects on the immune system. The immune response is a major factor in the pathogenesis of acute respiratory syncytial virus (RSV) infection. We hypothesised that there is a relationship between the neuroendocrine response in acute RSV infection, the severity of illness, and the degree of lymphopenia.. Prospective, non-randomised cohort study of infants hospitalised for RSV infection requiring mechanical ventilation or managed conservatively. The study assessed the effect of age, gender, birth gestation, and severity of illness on stress hormone profile and its relationship to lymphocyte count.. Regional Paediatric Intensive Care Unit (PICU) and children's wards.. Thirty-two consecutive infants with RSV infection were enrolled, of which thirteen were mechanically ventilated on PICU (study subjects) and nineteen treated on the ward (comparison group). Twenty-three children (72%) returned for follow-up.. A specific neuroendocrine profile was found in PICU patients compared to ward patients (Wilks Lambda = 0.36, F = 9.05, P =.03). PICU patients had significantly higher prolactin and growth hormone, and significantly lower leptin and IGF-1. Cortisol levels were the same. PICU patients were more lymphopenic compared to ward patients (P =.0001). On multiple regression analysis, prolactin and leptin levels accounted for 57% of the variation in lymphocyte count.. Whereas the effect of intensive care (mechanical ventilation and medication) could not be controlled for, our results suggest that there is an association between the neuroendocrine hormone response, severity of illness and degree of lymphopenia.

Topics: Acute Disease; Analysis of Variance; Bronchiolitis; Female; Humans; Hydrocortisone; Infant; Intensive Care Units, Pediatric; Leptin; Lymphopenia; Male; Neuroimmunomodulation; Neurosecretory Systems; Prolactin; Respiration, Artificial; Respiratory Syncytial Virus Infections; Severity of Illness Index

GH treatment can increase the mortality and morbidity of critically ill patients. The mechanisms of these harmful effects of GH are unknown but have been, in part, ascribed to interactions between GH and the immune system. Because GH has pattern-dependent actions we have now compared the dose-related effects of continuous and intermittent GH treatment given with or without an endotoxin (lipopolysaccharide; LPS) challenge. Male Wistar rats (n=6 per group) were treated for 5 days with recombinant human GH (0, 10, 100 or 1000 microg/kg per day) using either continuous s.c. infusion by osmotic minipump or intermittent twice daily s.c. injections. On day 4, endotoxin (5 mg/kg, i.p.) was injected and the animals monitored for a further 16 h. LPS administration alone led to neutrophilia and lymphopoenia, with increased plasma concentrations of urea, cholesterol, triglyceride, insulin and leptin, and decreased levels of IGF-I. High dose GH infusion (1000 microg/kg per day) followed by LPS caused greater increases in plasma urea, cholesterol, triglyceride, sodium and magnesium, but lower plasma glucose and insulin levels, than treatment with LPS alone. In contrast, twice daily injections of GH did not enhance these effects of endotoxin. In conclusion, the effects of endotoxin on plasma electrolytes, lipids, urea, glucose and insulin are differentially affected by the pattern of GH administration in the rat.

Topics: Animals; Bacterial Infections; Blood Glucose; Cholesterol; Dose-Response Relationship, Drug; Electrolytes; Human Growth Hormone; Infusion Pumps, Implantable; Injections, Subcutaneous; Insulin; Insulin-Like Growth Factor I; Leptin; Lipopolysaccharides; Lymphopenia; Magnesium; Male; Models, Animal; Rats; Rats, Wistar; Sodium; Triglycerides; Urea