transforming-growth-factor-beta and Respiration-Disorders

Transforming growth factor-beta (TGF-beta), a ubiquitous and multifunctional cytokine, is central to the evolution and modulation of host defense. Early on, TGF-beta was recognized for its chemotactic and pro-inflammatory properties, but then identification of its powerful suppressive activities focused attention on dissecting its mechanisms of immune inhibition. Just as quickly as TGF-beta-mediated regulation of a population of CD4(+)CD25(+)Foxp3(+) regulatory T cells became the rage, a surprising finding that TGF-beta was the impetus behind a subset of pro-inflammatory T helper (Th)17 cells brought back a re-emphasis on its broader ability to dictate inflammatory events. Emerging evidence indicates that much remains to be discovered regarding the complex and intertwined roles of TGF-beta in inflammation, T cell lineage commitment, antibody generation, immune suppression, and tolerance. While it may appear that TGF-beta has multiple, ill-defined, contradictory and overlapping modes of activity that are impossible to unravel, the current excitement for dissecting how TGF-beta controls immunity defines a challenge worthy of pursuit. The lung is particularly vulnerable to the influences of TGF-beta, which is produced by its immune and non-immune cell populations. In its absence, lung pathology becomes lethal, whereas TGF-beta overproduction also has untoward consequences, potentially leaving one breathless, and underscoring the paradoxical, but essential contribution of TGF-beta to tissue and immune homeostasis.

Topics: Animals; Antibody Formation; Cell Differentiation; Humans; Immune Tolerance; Inflammation Mediators; Respiration; Respiration Disorders; T-Lymphocyte Subsets; Transforming Growth Factor beta

Transforming growth factor-beta (TGF-beta) is a peptide implicated in tissue injury and repair but its role in the premature human lung remains unclear. In the present study, we used a TGF-beta responsive-promoter-luciferase construct in mink lung epithelial cells to quantify levels of biologically active TGF-beta (BA-TGF-beta) in the endotracheal aspirate (ETA) fluid from 16 extremely low birthweight neonates [6 M/10 F, mean GA 26 weeks (range 23-30), mean BW 774 g (range 555-1,075)]. ETA fluid was obtained on day 1 and then every 4 days up to 32 days. BA-TGF-beta levels were low (92 +/- 19 pg/ml) in the first 24 h of life and then increased 5- to 10-fold with peak BA-TGF-beta levels (400 +/- 50 pg/ml) on day 20-25. BA-TGF-beta levels were higher in male than female infants (p = 0.0056). Prenatal steroids decreased significantly the amount of BA-TGF-beta recovered. High initial levels of BA-TGF-beta persisted over time and were predictive of the need for oxygen therapy at home. We conclude that abundant BA- TGF-beta is present in the lungs of preterm infants and speculate that it may be involved in inflammatory and repair processes encountered in acute and chronic lung disease.

Topics: Bronchoalveolar Lavage Fluid; Cell Count; Female; Home Care Services; Humans; Infant, Low Birth Weight; Infant, Newborn; Lung; Macrophages; Male; Oxygen; Prognosis; Respiration Disorders; Sex Characteristics; Transforming Growth Factor beta