vasoactive-intestinal-peptide and Respiratory-Distress-Syndrome--Newborn

The pathogenesis of tissue injury in disease is a complex process that is only partially understood. We have investigated different models of acute lung injury, representing the clinical entity known as the acute respiratory distress syndrome, and tested their possible modulation by the neuropeptide vasoactive intestinal peptide (VIP). Three major mechanisms of injury appear to be involved in many of these models as common denominators: (1) activation of nuclear transcriptions factor NFkappaB; (2) apoptotic cell death; and (3) excitotoxic phenomena, due to activation of N-methyl-D-aspartate glutamate receptors. These pathogenetic mechanisms and pathways are logical targets of therapeutic intervention. Protection by VIP against lung injury, and against related forms of injury/cell death of neuronal cells and heart muscle, is attributable, in large measure, to the ability of VIP to suppress these mechanisms, and to additional anti-inflammatory and anti-oxidant actions. Finally, a hypothesis is presented for survival-promoting pathways that can be augmented by VIP and the related pituitary adenylyl cyclase-activating peptide.

Topics: Animals; Apoptosis; Cell Survival; Humans; Infant, Newborn; Lung; Lung Injury; Pneumonia; Respiratory Distress Syndrome, Newborn; Signal Transduction; Vasoactive Intestinal Peptide

The quantitative distribution of bombesin- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities was determined by RIA and immunocytochemistry in regions of trachea, bronchus, and whole lung at various stages of human fetal development and in neonates, children, and adults. In addition, these two immunoreactivities were studied in infants that had died of the acute respiratory distress syndrome. The concentration of bombesin-like immunoreactivity in the whole respiratory tract steadily increased during gestation, reaching a plateau at birth. In the lung, the bombesin concentration remained almost unchanged during childhood, but decreased to one tenth in the adult. In neonates with the acute respiratory distress syndrome, there was a significantly lower bombesin content in all regions of the respiratory tract compared to either normal full-term infants or 24- to 28-week-old fetuses. Immunocytochemistry localized bombesin immunoreactivity within mucosal neuroendocrine cells present in the airway epithelium throughout the respiratory tract and particularly in the intrapulmonary airways. The number of cells increased throughout gestation, reflecting the pattern found by RIA, and were greatly decreased in acute respiratory distress syndrome patients. VIP concentrations were much lower than those of bombesin and did not change significantly with gestational age. In contrast to bombesin, VIP was mainly concentrated in the upper respiratory tract. In infants with the respiratory distress syndrome, the VIP content was not different from normal. These results are compatible with the possibility that bombesin-like peptides may have a role in the normal development of the human lung.

Topics: Acute Disease; Adolescent; Adult; Aged; Bombesin; Child; Child, Preschool; Gestational Age; Histocytochemistry; Humans; Immunoassay; Infant; Infant, Newborn; Lung; Middle Aged; Peptides; Respiratory Distress Syndrome, Newborn; Respiratory System; Tissue Distribution; Vasoactive Intestinal Peptide