neuropeptide-y and Escherichia-coli-Infections

Within the immunosuppressive ocular microenvironment, there are constitutively present the immunomodulating neuropeptides alpha-melanocyte stimulating hormone (α-MSH) and neuropeptide Y (NPY) that promote suppressor functionality in macrophages. In this study, we examined the possibility that α-MSH and NPY modulate phagocytic activity in macrophages. The macrophages treated with α-MSH and NPY were significantly suppressed in their capacity to phagocytize unopsonized Escherichia coli and Staphylococcus aureus bioparticles, but not antibody-opsonized bioparticles. The neuropeptides significantly suppressed phagolysosome activation, and the FcR-associated generation of reactive oxidative species as well. This suppression corresponds to neuropeptide modulation of macrophage functionality within the ocular microenvironment to suppress the activation of immunogenic inflammation.

Topics: alpha-MSH; Animals; Cell Line, Tumor; Escherichia coli; Escherichia coli Infections; Leukemia, Monocytic, Acute; Macrophages; Mice; Neuroimmunomodulation; Neuropeptide Y; Phagocytosis; Phagosomes; Reactive Oxygen Species; Retina; Staphylococcal Infections; Staphylococcus aureus

To evaluate the possible effects of a combination of systemic nitric oxide synthesis inhibition (to increase mean arterial blood pressure) and nitric oxide inhalation (to decrease pulmonary vascular pressure) in porcine endotoxin shock.. Prospective trial.. Laboratory at a large university medical center.. Ten pathogen-free pigs weighing 19 to 25 kg.. After surgical preparation, all pigs received a continuous infusion of Escherichia coli lipopolysaccharide endotoxin (15 micrograms/kg/hr) for 2 hrs. After 1 hr of endotoxemia, nitric oxide inhalation (50 parts per million) and NG-nitro-L-arginine infusion (50 mg/kg/hr) were initiated in six pigs. Four pigs served as controls and received only a lipopolysaccharide infusion.. NG-nitro-L-arginine infusion and nitric oxide inhalation prevented the further decrease in mean arterial blood pressure seen in the control pigs (p < .05), but did not restore mean arterial blood pressure back to basal values. Cardiac output decreased significantly compared with controls during NG-nitro-L-arginine infusion/nitric oxide inhalation (p < .01). Systemic vascular resistance, which was below basal values in the controls after 2 hrs of endotoxemia, was markedly increased by NG-nitro-L-arginine/nitric oxide, to higher values than those observed in the basal state (p < .01). In the control pigs, mean pulmonary arterial pressure and pulmonary vascular resistance showed a biphasic increase. In the NG-nitro-L-arginine/nitric oxide treated group, the second phase increase in mean pulmonary arterial pressure did not occur (p < .01). However, there was no difference in pulmonary vascular resistance between the groups. Renal vascular resistance was unchanged in controls, while NG-nitro-L-arginine/nitric oxide induced a four-fold increase in renal vascular resistance (p < .001). There was no statistical difference in urine production between the groups. PaO2 values were higher and PaCO2 tensions were lower in the treated pigs than in the controls. Arterial pH and base excess did not differ. Arterial plasma epinephrine, norepinephrine, and neuropeptide Y concentrations increased during the lipopolysaccharide infusion in both groups, with a tendency toward higher concentrations in the pigs receiving NG-nitro-L-arginine/nitric oxide. Arterial plasma endothelin-1-like immunoreactivity in these pigs was significantly higher at the end of the treatment than in the controls.. In this model of porcine endotoxin shock, the combination of NG-nitro-L-arginine infusion and nitric oxide inhalation attenuated pulmonary hypertension and improved gas exchange; it also prevented development of further systemic hypotension, but impaired cardiac output and increased systemic and renal vascular resistances to supranormal levels. NG-nitro-L-arginine/nitric oxide did not reduce sympathetic nervous system activation or metabolic acidosis.

Topics: Administration, Inhalation; Animals; Arginine; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endothelins; Escherichia coli Infections; Female; Infusions, Intravenous; Male; Neuropeptide Y; Nitric Oxide; Nitroarginine; Shock, Septic; Specific Pathogen-Free Organisms; Swine