Tumour necrosis factor-alpha inhibits synthesis of surfactant by isolated human type II pneumocytes

Abstract

Objective: To investigate the effect of tumour necrosis factor-alpha (TNF-alpha) on the synthesis of surfactant by human type II pneumocytes.

Design: Laboratory study.

Setting: University departments of surgery and biochemistry.

Material: Segments of right lower lobe of lungs from nine donors of other organs, and from tumour-free portions of 10 lungs excised from patients with lung cancer.

Main outcome measures: Effect of TNF-alpha on the incorporation of D-glucose and palmitate, both of which had been uniformly labelled with 14C (D-(U-14C) glucose and (U-14C) palmitate), into various phospholipid fractions by pneumocytes isolated from both healthy lungs and those from patients with lung cancer.

Results: TNF-alpha decreased the incorporation of both D-(U-14C) glucose and (U-14C) palmitate into phospholipid fractions, particularly phosphatidylcholine, in both healthy lung tissue and that from patients with lung cancer. The degree of inhibition was less in the group from patients with lung cancer because the basal value was lower.

Conclusion: TNF-alpha may contribute to the pathophysiology of the adult respiratory distress syndrome by inhibiting the synthesis of surfactant. The results suggest the possibility that TNF-alpha may be produced locally in the presence of lung cancer resulting in chronic paracrine or systemic exposure of pneumocytes to low concentrations of the cytokine.