Elsevier

Respiratory Medicine

Volume 91, Issue 1, January 1997, Pages 31-39
Respiratory Medicine

Original article
Thalidomide reduces tumour necrosis factor-α production by human alveolar macrophages

https://doi.org/10.1016/S0954-6111(97)90134-7Get rights and content
Under an Elsevier user license
open archive

Abstract

Overexuberant production of tumour necrosis factor-α (TNF-α) by macrophages and other cells is thought to contribute to the development of permanent lung damage in many inflammatory conditions. There is a need for an agent, without the side-effects of corticosteroids, which can reduce the production of TNF-α by macrophages activated by disease. This study evaluated the effect of thalidomide on lipopolysaccharide (LPS)-induced TNF-α production by human alveolar macrophages obtained from patients with tuberculosis and a group of other diseases associated with macrophage activation.

Alveolar macrophages obtained by bronchoalveolar lavage from 31 patients (tuberculosis=12, sarcoidosis=3, lung cancer =5, chronic bronchitis=5, pneumonia=6) were stimulated with LPS alone or LPS in combination with either thalidomide or dexamethasone. Cell-associated TNF-α, as measured by immunochemistry, and TNF-α released by macrophages, as assessed by ELISA, were markedly increased when cells were incubated with LPS (P<0·05), and both were decreased following addition of thalidomide (P<0·05) or dexamethasone (P<0·05) to amounts similar to those observed when macrophages were incubated with medium alone. Similarly, TNF-α mRNA as measured by in situ hybridization was increased following incubation with LPS (P<0·05), but this increase was prevented by addition of thalidomide (P<0·05) or dexamethasone (P<0·05). The ability of thalidomide to reduce LPS-induced TNF-α production by alveolar macrophages was the same when cells from patients with tuberculosis (a disease associated with TNF-α production) and cells from patients with the other conditions were compared.

The ability of thalidomide to reduce TNF-α production by human alveolar macrophages from patients with active lung disease suggests that thalidomide and its analogues may have potential as drugs to reduce TNF-α production in disease.

Cited by (0)

Present address: Faculdade de Ciencias Medicas, Universidade do Estado do Rio de Janeiro, Avenida 28 de Setembro, no 87, Vila Isabel Rio de Janeiro, Rio de Janeiro, Brazil.