Evaluation of the in vitro and in vivo effects of cyclosporine on the lung T-lymphocyte alveolitis of active pulmonary sarcoidosis. Academic Article uri icon

Overview

MeSH

  • Adult
  • Cells, Cultured
  • Female
  • Humans
  • Inflammation
  • Lymphocyte Activation
  • Male
  • T-Lymphocytes

MeSH Major

  • Cyclosporins
  • Lung
  • Lung Diseases
  • Pulmonary Alveoli
  • Sarcoidosis

abstract

  • Pulmonary sarcoidosis is a granulomatous disorder characterized by the accumulation of activated helper/inducer T-lymphocytes in the lower respiratory tract, a process thought to be central to the pathogenesis of the disease. Because cyclosporine, a fungus-derived cyclic peptide, has specific inhibitory effects on T-lymphocyte activation, it should suppress activated sarcoid lung T-cells, and thus it should theoretically be an ideal therapeutic agent for sarcoidosis. This was confirmed in vitro: the addition of cyclosporine to T-cells recovered from the lungs of patients with active sarcoid suppressed the spontaneous release of interleukin-2 (IL-2) and monocyte chemotactic factor by these cells and inhibited their exaggerated spontaneous replication. In contrast, the oral administration of conventional doses (10 mg/kg/day) of cyclosporine to eight of these patients over a 6-month period was not accompanied by suppression of sarcoid lung T-cell activation. On the average, the spontaneous release of IL-2 and monocyte chemotactic factor, the proliferation of lymphocytes, and the number of helper/inducer T-cells present in the lungs of these subjects remained elevated and similar to their pretherapy values. Consistent with this lack of effect on sarcoid lung T-cell activation, no improvement in lung function was observed over the trial period. Thus, although cyclosporine is effective in vitro in suppressing the exaggerated activation of sarcoid lung T-cells, it does not do so in vivo, suggesting this agent will not be useful in the therapy of active pulmonary sarcoidosis, at least when administered in a conventional fashion.

publication date

  • November 1988

has subject area

  • Adult
  • Cells, Cultured
  • Cyclosporins
  • Female
  • Humans
  • Inflammation
  • Lung
  • Lung Diseases
  • Lymphocyte Activation
  • Male
  • Pulmonary Alveoli
  • Sarcoidosis
  • T-Lymphocytes

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1164/ajrccm/138.5.1242

PubMed ID

  • 3264483

Additional Document Info

start page

  • 1242

end page

  • 1248

volume

  • 138

number

  • 5