Elsevier

Clinical Immunology

Volume 99, Issue 3, June 2001, Pages 308-319
Clinical Immunology

Short Analytical Review
Fibrosis of the Lung and Other Tissues: New Concepts in Pathogenesis and Treatment

https://doi.org/10.1006/clim.2001.5008Get rights and content

Abstract

Tissue fibrosis can lead to significant organ dysfunction and resulting patient morbidity and mortality. Unfortunately, the therapeutic repertoire is currently limited, nonspecific, and largely ineffective. While the pathogenesis is incompletely understood, evidence is accumulating that immune and cytokine mediated mechanisms are critical. In this review, data will be provided to support the role of Type 2 cytokines in the pathogenesis of fibrosis. The importance of the role of the pro-fibrogenic cytokine TGF-β and CD40–CD40 ligand mediated fibroblast activation will also be evaluated. Finally, novel therapeutic options based on inhibiting these pathways will be described.

References (104)

  • K. Miyazono et al.

    Latent high molecular weight complex of transforming growth factor β1: Purification from human platelets and structural characterization

    J. Biol. Chem.

    (1988)
  • S.M. Wahl et al.

    Inflammatory and immunomodulatory roles of TGFβ

    Immunol. Today

    (1989)
  • J.J. Letterio et al.

    Molecule of the month. TGFβ; A key modulator of immune cell function

    Clin. Immunol. Immunopathol.

    (1997)
  • A. Desmouliere et al.

    Apoptosis during wound healing, fibrocontractive diseases and vascular wall injury

    Int. J. Biochem. Cell. Biol.

    (1997)
  • C.E. Rube et al.

    Dose-dependent induction of transforming growth factor beta (TGF-beta) in the lung tissue of fibrosis-prone mice after thoracic irradiation

    Int. J. Radiat. Oncol. Biol. Phys.

    (2000)
  • P.J. Sime et al.

    Transient gene transfer and expression in the lung

    Chest

    (1997)
  • J.S. Munger et al.

    The integrin alpha v beta 6 binds and activates latent TGF beta1: A mechanism for regulating pulmonary inflammation and fibrosis

    Cell

    (1999)
  • P.J. Sime et al.

    Transfer of tumor necrosis factor-alpha to rat lung induces severe pulmonary inflammation and patchy interstitial fibrogenesis with induction of transforming growth factor-beta1 and myofibroblasts

    Am. J. Pathol.

    (1998)
  • A. Logan et al.

    Decorin attenuates gliotic scar formation in the rat cerebral hemisphere

    Exp. Neurol.

    (1999)
  • K.M. Fries et al.

    CD40 expression by human fibroblasts

    Clin. Immunol. Immunopathol.

    (1995)
  • Y. Zhang et al.

    CD40 engagement up-regulates cyclooxygenase-2 expression and prostaglandin E2 production in human lung fibroblasts

    J. Immunol.

    (1998)
  • R.P. Phipps et al.

    A new view of prostaglandin E regulation of the immune response

    Immunol. Today

    (1991)
  • A. Adawi et al.

    Blockade of CD40–CD40 ligand interactions protects against radiation-induced pulmonary inflammation and fibrosis

    Clin. Immunol. Immunopathol.

    (1998)
  • P.A. Ward et al.

    Lung inflammation and fibrosis

    Am. J. Respir. Crit. Care Med.

    (1998)
  • 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.E. Postlethwaite et al.

    Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4

    J. Clin. Invest.

    (1992)
  • G.D. Sempowski et al.

    Subsets of murine lung fibroblasts express membrane-bound and soluble IL-4 receptors. Role of IL-4 in enhancing fibroblast proliferation and collagen synthesis

    J. Immunol.

    (1994)
  • M.R. Duncan et al.

    Gamma interferon is the lymphokine and beta interferon the monokine responsible for inhibition of fibroblast collagen production and late but not early fibroblast proliferation

    J. Exp. Med.

    (1985)
  • G.D. Sempowski et al.

    Interleukin-4 and interferon-gamma discordantly regulate collagen biosynthesis by functionally distinct lung fibroblast subsets

    J. Cell. Physiol.

    (1996)
  • H.A. Jaffe et al.

    Selective inhibition of collagen gene expression in fibroblasts by an interferon-gamma transgene

    Exp. Lung Res.

    (1999)
  • C. Buttner et al.

    Local production of interleukin-4 during radiation-induced pneumonitis and pulmonary fibrosis in rats: Macrophages as a prominent source of interleukin-4

    Am. J. Respir. Cell. Mol. Biol.

    (1997)
  • W. Westermann et al.

    Th2 cells as effectors in postirradiation pulmonary damage preceding fibrosis in the rat

    .Int. J. Radiat. Biol.

    (1999)
  • M. Gharaee-Kermani et al.

    Lung interleukin-5 expression in murine bleomycin-induced pulmonary fibrosis

    Am. J. Respir. Cell. Mol. Biol.

    (1997)
  • K. Zhang et al.

    Lung monocyte chemoattractant protein-1 gene expression in bleomycin-induced pulmonary fibrosis

    J. Immunol.

    (1994)
  • M. Gharaee-Kermani et al.

    The role of IL-5 in bleomycin-induced pulmonary fibrosis

    J. Leukocyte Biol.

    (1998)
  • R.E. Smith

    Chemotactic cytokines mediate leukocyte recruitment in fibrotic lung disease

    Biol. Signals

    (1996)
  • F. Huaux et al.

    Lung fibrosis induced by silica particles in NMRI mice is associated with an upregulation of the p40 subunit of interleukin-12 and Th-2 manifestations

    Am. J. Respir. Cell. Mol. Biol.

    (1999)
  • F. Huaux et al.

    Role of interleukin-10 in the lung response to silica in mice

    Am. J. Respir. Cell. Mol. Biol.

    (1998)
  • G.S. Davis et al.

    Interferon-gamma production by specific lung lymphocyte phenotypes in silicosis in mice

    Am. J. Respir. Cell. Mol. Biol.

    (2000)
  • H. Furuie et al.

    Altered accessory cell function of alveolar macrophages: A possible mechanism for induction of Th2 secretory profile in idiopathic pulmonary fibrosis

    Eur. Respir. J.

    (1997)
  • S.P. Atamas et al.

    Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis

    Arthritis Rheum.

    (1999)
  • H.N. Antoniades et al.

    Expression of monocyte chemoattractant protein 1 mRNA in human idiopathic pulmonary fibrosis

    Proc. Natl. Acad. Sci. USA

    (1992)
  • A. Hancock et al.

    Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung

    Am. J. Respir. Cell. Mol. Biol.

    (1998)
  • M. Suga et al.

    Clinical significance of MCP-1 levels in BALF and serum in patients with interstitial lung diseases

    Eur. Respir. J.

    (1999)
  • D. Petovka et al.

    Evaluation of CD30 as a marker for Th2 lymphocytes in bronchoalveolar lavage in interstitial lung diseases

    Respir. Med.

    (2000)
  • W.A. Wallace et al.

    A type 2 (Th2-like) pattern of immune response predominates in the pulmonary interstitium of patients with cryptogenic fibrosing alveolitis (CFA)

    Clin. Exp Immunol.

    (1995)
  • S. Majumdar et al.

    Different cytokine profiles in cryptogenic fibrosing alveolitis and fibrosing alveolitis associated with systemic sclerosis

    Eur. Respir. J.

    (1999)
  • L. Boulet et al.

    Airway responsiveness and bronchial-wall thickness in asthma with or without fixed airflow obstruction

    Am. J. Respir. Crit. Care Med.

    (1995)
  • K. Shigehara et al.

    Increased levels of interleukin-18 in patients with pulmonary sarcoidosis

    Am. J. Respir. Crit. Care Med.

    (2000)
  • D.S. Kim et al.

    The value of interleukin-12 as an activity marker of pulmonary sarcoidosis

    Sarc. Vasc. Diffuse Lung Dis.

    (2000)
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