2008; doi:10.1152/ajpendo.90263.2008.-Oxytocin is a hormone and neurotransmitter found to have anti-inflammatory functions in rodents. Here we used experimental bacterial endotoxinemia to examine the role of exogenous oxytocin administration on innate immune responses in humans. Ten healthy men received, in a randomized, placebo-controlled, crossover design, placebo, oxytocin, LPS, and LPS ϩ oxytocin. Oxytocin treatment resulted in a transient or prolonged reduction of endotoxin-induced increases in plasma ACTH, cortisol, procalcitonin, TNF-␣, IL-1 receptor antagonist, IL-4, IL-6, macrophage inflammatory protein-1␣, macrophage inflammatory protein-1␤, monocyte chemoattractant protein-1 (MCP-1), interferoninducible protein 10, and VEGF. In vitro, oxytocin had no impact on LPS effects in releasing TNF-␣, IL-6, and MCP-1 in monocytes and peripheral blood mononuclear cells from healthy human donors. In summary, oxytocin decreases the neuroendocrine and cytokine activation caused by bacterial endotoxin in men, possibly due to the pharmacological modulation of the cholinergic anti-inflammatory pathway. Oxytocin might be a candidate for the therapy of inflammatory diseases and conditions associated with high cytokine and VEGF levels.neuroendocrinology; hypothalamic-pituitary-adrenal; cytokines SYSTEMIC INFLAMMATION IS IMPLICATED in the pathophysiology of many diseases, including chronic inflammatory diseases, infections, sepsis, atherosclerosis, and obesity (11,13,22,25). The most widely used model for testing the systemic host response to infection and inflammation in humans is the intravenous administration of bacterial endotoxin, which contains LPS parts of the Escherichia coli bacterial wall (8). Human response mechanisms to this challenge are integrated via coordinated neuroendocrine-immune interactions (5, 9, 30).Physiological conditions associated with a reduced hypothalamic-pituitary-adrenal (HPA) response to different stressors include the peripartal period and lactation (12,26). Common denominators of these conditions are high intrahypothalamic and plasma oxytocin concentrations. Oxytocin is a highly conserved nonapeptide with hormone and neurotransmitter properties that is synthesized in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus (10). It exerts direct excitatory effects on vagal neurons and has classic reproduction-related functions (1,14,20).A large body of evidence suggests a regulatory role of oxytocin during immune and inflammatory responses in animal models. Oxytocin displays anti-inflammatory effects, abolishes the sepsis-induced increase in TNF-␣, and protects against multiple organ damage (6, 7, 16, 24). In contrast, oxytocindeficient mice exhibit increased stress responses associated with a significant hyperactivation of the HPA axis (2).Here we present a randomized, placebo-controlled, crossover trial, conducted to test the effect of continuous intravenous oxytocin infusion on LPS-induced systemic inflammation in 10 healthy men. In addition, we investigated whether ...

Background Currently, no estimates can be made on the impact of hematopoietic stem cell transplantation on allergy transfer or cure of the disease. By using component‐resolved diagnosis, we prospectively investigated 50 donor‐recipient pairs undergoing allogeneic stem cell transplantation. This allowed calculating the rate of transfer or maintenance of allergen‐specific responses in the context of stem cell transplantation. Methods Allergen‐specific IgE and IgG to 156 allergens was measured pretransplantation in 50 donors and recipients and at 6, 12 and 24 months in recipients post‐transplantation by allergen microarray. Based on a mixed effects model, we determined risks of transfer of allergen‐specific IgE or IgG responses 24 months post‐transplantation. Results After undergoing stem cell transplantation, 94% of allergen‐specific IgE responses were lost. Two years post‐transplantation, recipients' allergen‐specific IgE was significantly linked to the pretransplantation donor or recipient status. The estimated risk to transfer and maintain individual IgE responses to allergens by stem cell transplantation was 1.7% and 2.3%, respectively. Allergen‐specific IgG, which served as a surrogate marker of maintaining protective IgG responses, was highly associated with the donor's (31.6%) or the recipient's (28%) pretransplantation response. Conclusion Hematopoietic stem cell transplantation profoundly reduces allergen‐specific IgE responses but also comes with a considerable risk to transfer allergen‐specific immune responses. These findings facilitate clinical decision‐making regarding allergic diseases in the context of hematopoietic stem cell transplantation. In addition, it provides prospective data to estimate the risk of transmitting allergen‐specific responses via hematopoietic stem cell transplantation.

Background: Delayed food anaphylaxis upon consumption of red meat is attributed to specific IgE-antibodies directed to galactose-α-1,3-galactose (α-Gal). Anaphylactic reactions may occur after ingestion of meat from different mammals, mainly beef and pork, but reactions to lamb, rabbit or horse have also been reported. In particular, pork kidney has been shown to trigger symptoms that were more severe and occurred within a shorter delay. The objective of the present study was the identification and characterization of pork kidney proteins carrying α-Gal carbohydrates and mediating delayed allergic reactions through specific IgE to α-Gal. Materials and methods: A cohort of 59 patients with specific IgE to α-Gal was screened by immunoblot for IgE-reactive proteins in pork kidney extract. Proteins were purified by affinity chromatography and identified by Edman sequencing and peptide mass fingerprinting. Isolated proteins were used in immunoassays using patient sera and α-Gal specific antibodies. Allergenicity was assayed in basophil activation and skin prick test. Results: Multiple IgE-binding proteins were detected in protein extracts of pork kidney by immunoblot using patient sera and an anti-α-Gal antibody. Reactive bands were located in the high molecular weight range of 100 to ≥200 kDa. Two major IgE-binding proteins were identified as porcine angiotensin I converting enzyme (ACE I) and aminopeptidase N (AP-N). IgE-binding to both proteins was lost by periodate treatment, resulting in oxidation of carbohydrates. Addition of α-Gal inhibited IgE-reactivity to both peptidases. Allergenicity was confirmed by activation of patient basophils and positive skin prick tests. Conclusions: Two IgE-reactive cell membrane peptidases carrying α-Gal epitopes were identified in pork kidney, a tissue which is known as potent inducer of red meat-induced anaphylaxis. Allergenicity and clinical relevance of these proteins were confirmed in patients with delayed anaphylaxis to red meat by skin prick test and basophil activation.