Serial Review: Redox signaling in immune function and cellular responses in lung injury and diseases Serial Review Editors: Victor Darley–Usmar, Lin Mantell
Cytokines in tolerance to hyperoxia-induced injury in the developing and adult lung

https://doi.org/10.1016/j.freeradbiomed.2006.01.027Get rights and content

Abstract

Cytokines are peptides that are produced by virtually every nucleated cell type in the body, possess overlapping biological activities, exert different effects at different concentrations, can either synergize or antagonize the effects of other cytokines, are regulated in a complex manner, and function via cytokine cascades. Hyperoxia-induced acute lung injury (HALI) is characterized by an influx of inflammatory cells, increased pulmonary permeability, and endothelial and epithelial cell injury/death. Some of these effects are orchestrated by cytokines. There are significant differences in the response of the developing versus the adult lung to hyperoxia. We review here cytokines (and select growth factors) that are involved in tolerance toward HALI in animal models. Increased cytokine expression and release have a cascade effect in HALI. IL-1 precedes the increase in IL-6 and CINC-1/IL-8 and this seems to predate the influx of inflammatory cells. Inflammatory cells in the alveolar space amplify the lung damage. Other cytokines that are primarily involved in this inflammatory response include IFN-γ, MCP-1, and MIP-2. Certain cytokines (and growth factors) seem to ameliorate HALI by affecting cell death pathways. These include GM-CSF, KGF, IL-11, IL-13, and VEGF. There are significant differences in the type and temporal sequence of cytokine expression and release in the adult and newborn lung in response to hyperoxia. The newborn lung is greatly resistant to hyperoxia compared to the adult. The delayed increase in lung IL-1 and IL-6 in the newborn could induce protective factors that would help in the resolution of hyperoxia-induced injury. Designing a therapeutic approach to counteract oxygen toxicity in the adult and immature lung first needs understanding of the unique responses in each scenario.

Section snippets

Mechanism(s) of tissue injury/cell death in HALI

At sites of tissue injury, cells can die via necrosis or apoptosis. Traditionally, these processes have been considered operationally and mechanistically distinct cell-death responses [27], [28]. This distinction may not be as clear-cut as previously thought [29]. Studies have shown that apoptosis-like deoxyribonucleic acid (DNA) laddering and positive terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining can be seen in cells undergoing necrosis. Known inducers of

Cytokines (and select growth factors) involved in tolerance toward HALI

In this review, we will focus on cytokines (and select growth factors) that have been shown to be involved in tolerance toward HALI in animal models.

Conclusions

It is quite apparent that cytokines (and growth factors) have a significant role to play in tolerance to hyperoxic lung injury. Increased cytokine expression and release have a cascade effect. IL-1 precedes the increase in IL-6 and IL-8 and this seems to precede the influx of inflammatory cells. It is possible that resident cells in the lung initiate the inflammatory response to hyperoxia by the release of various cytokines, which, in turn, attract inflammatory cells to the alveolar space and

Acknowledgments

This work was supported in part by Grants HL-74195 (V.B.), HL-64242, HL-61904, and HL-56389 (J.A.E.) from the NHLBI of the National Institutes of Health, USA.

References (138)

  • A. Dunican et al.

    Neutrophils regulate their own apoptosis via preservation of CXC receptors

    J. Surg. Res.

    (2000)
  • M. Hu et al.

    Transmigration across a lung epithelial monolayer delays apoptosis of polymorphonuclear leukocytes

    Surgery

    (2004)
  • J.D. Hasday et al.

    Febrile-range hyperthermia augments pulmonary neutrophil recruitment and amplifies pulmonary oxygen toxicity

    Am. J. Pathol.

    (2003)
  • R. Paine et al.

    Transgenic overexpression of granulocyte macrophage-colony stimulating factor in the lung prevents hyperoxic lung injury

    Am. J. Pathol.

    (2003)
  • W.P. Arend

    Interleukin-1 receptor antagonist

    Adv. Immunol.

    (1993)
  • S.E. Welty et al.

    Hyperoxic increases in lung ICAM-1 mRNA are independent of TNF-α and IL-1β mRNA

    Free Radic. Biol. Med.

    (1997)
  • B. Piedboeuf et al.

    Interleukin-1 expression during hyperoxic lung injury in the mouse

    Free Radic. Biol. Med.

    (1998)
  • D.M. Guidot et al.

    Mitochondrial antioxidant function is a potential mechanism for organ differences in interleukin-1-mediated tolerance to oxidative injury

    Am. J. Med. Sci.

    (1999)
  • J.J. Haddad et al.

    Immunomodulatory potential of thymulin–Zn(2+) in the alveolar epithelium: amelioration of endotoxin-induced cytokine release and partial amplification of a cytoprotective IL-10-sensitive pathway

    Biochem. Biophys. Res. Commun.

    (2000)
  • R. Gavino et al.

    Release of cytokines and apoptosis in fetal rat type II pneumocytes exposed to hyperoxia and nitric oxide: modulatory effects of dexamethasone and pentoxifylline

    Cytokine

    (2002)
  • H. Tilg et al.

    Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55

    Blood

    (1994)
  • H.J. Lindsey et al.

    Pentoxifylline attenuates oxygen-induced lung injury

    J. Surg. Res.

    (1994)
  • J.J. Oppenheim

    Foreword

  • S.L. Kunkel et al.

    Cytokine networks and leukocyte recruitment

  • T.R. Mosmann et al.

    Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins

    J. Immunol.

    (1986)
  • A. O’Regan et al.

    Cytokines in cell-mediated immune responses

  • M.M. Rosenkilde et al.

    The chemokine system—A major regulator of angiogenesis in health and disease

    APMIS

    (2004)
  • M. Thelen

    Dancing to the tune of chemokines

    Nat. Immunol.

    (2001)
  • D. Rossi et al.

    The biology of chemokines and their receptors

    Annu. Rev. Immunol.

    (2000)
  • J.D. Crapo

    Morphologic changes in pulmonary oxygen toxicity

    Annu. Rev. Physiol.

    (1986)
  • B.B. Warner et al.

    Functional and pathological effects of prolonged hyperoxia in neonatal mice

    Am. J. Physiol.

    (1998)
  • J. Corne et al.

    IL-13 stimulates vascular endothelial cell growth factor and protects against hyperoxic acute lung injury

    J. Clin. Invest.

    (2000)
  • A.B. Waxman et al.

    Targeted lung expression of interleukin-11 enhances murine tolerance of 100% oxygen and diminishes hyperoxia-induced DNA fragmentation

    J. Clin. Invest.

    (1998)
  • I.I. Ekekezie et al.

    Monocyte chemoattractant protein-1 and its receptor CCR-2 in piglet lungs exposed to inhaled nitric oxide and hyperoxia

    Pediatr. Res.

    (2001)
  • J. Ben-Ari et al.

    Cytokine response during hyperoxia: sequential production of pulmonary tumor necrosis factor and interleukin-6 in neonatal rats

    Isr. Med. Assoc. J.

    (2000)
  • C.J. Johnston et al.

    Comparison of adult and newborn pulmonary cytokine mRNA expression after hyperoxia

    Exp. Lung Res.

    (1997)
  • D.S. Bonikos et al.

    Oxygen toxicity in the newborn: the effect of chronic continuous 100 percent oxygen exposure on the lungs of newborn mice

    Am. J. Pathol.

    (1976)
  • L. Frank et al.

    Oxygen toxicity in neonatal and adult animals of various species

    J. Appl. Physiol.

    (1978)
  • K.A. Veness-Meehan et al.

    Temporal and spatial expression of biglycan in chronic oxygen-induced lung injury

    Am. J. Respir. Cell Mol. Biol.

    (1994)
  • C.T. D’Angio et al.

    Changes in surfactant protein gene expression in a neonatal rabbit model of hyperoxia-induced fibrosis

    Am. J. Physiol.

    (1997)
  • S.C. Langley et al.

    Depletion of pulmonary glutathione using diethylmaleic acid accelerates the development of oxygen-induced lung injury in term and preterm guinea-pig neonates

    J. Pharm. Pharmacol.

    (1994)
  • Y. Chen et al.

    Comparative responses of premature versus full-term newborn rats to prolonged hyperoxia

    Pediatr. Res.

    (1994)
  • H.J. Rozycki et al.

    Cytokines and oxygen radicals after hyperoxia in preterm and term alveolar macrophages

    Am. J. Physiol. Lung Cell Mol. Physiol.

    (2002)
  • H.J. Rozycki et al.

    Effect of hyperoxia on interleukin-8 expression in premature versus term rabbit lung explants

    Exp. Lung Res.

    (2004)
  • J.J. Coalson et al.

    Neonatal chronic lung disease in extremely immature baboons

    Am. J. Respir. Crit. Care Med.

    (1999)
  • J.J. Cohen

    Apoptosis and its regulation

    Adv. Exp. Med. Biol.

    (1996)
  • G. Kroemer et al.

    The biochemistry of programmed cell death

    FASEB J.

    (1995)
  • A. Pagano et al.

    Alveolar cell death in hyperoxia-induced lung injury

    Ann. N. Y. Acad. Sci.

    (2003)
  • B.D. Uhal et al.

    Fibroblasts isolated after fibrotic lung injury induce apoptosis of alveolar epithelial cells in vitro

    Am. J. Physiol.

    (1995)
  • N.S. Ward et al.

    Interleukin-6-induced protection in hyperoxic acute lung injury

    Am. J. Respir. Cell Mol. Biol.

    (2000)
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