INTERLEUKIN-1 IS LINKED TO THE RESPIRATORY EPITHELIAL CYTOPATHOLOGY OF PERTUSSIS

Bordetella pertussis, the causative agent of whooping cough, releases a muramyl peptide known as tracheal cytotoxin (TCT) that is responsibl e for destruction of ciliated epithelial cells lining the large airway s. In vitro, TCT has been shown to cause this specific pathology in hu man or hamster respiratory epithelium and to inhibit the proliferation of cultured hamster trachea epithelial cells. The diverse biological actions of maramyl peptides, including adjuvanticity, somnogenicity, a nd pyrogenicity, have been correlated with the production and release of the inflammatory mediator interleukin-1 (IL-1). Consistent with its ability to reproduce other muramyl peptide actions, recombinant IL-1 caused TCT-like damage to the respiratory epithelium. In the nanogram- per-milliliter range, exogenous IL-1 inhibited DNA synthesis in hamste r trachea epithelial cells and reproduced the pathology of TCT in hams ter tracheal organ culture. Tumor necrosis factor alpha and 1L-6, cyto kines also associated with inflammation, were unable to reproduce TCT cytopathology. Furthermore, exposure of respiratory epithelial cells t o TCT stimulated production of cell-associated IL-1alpha, which could be detected within 2 h of TCT treatment. In contrast, there was no evi dence of TCT-triggered release of IL-1. Previous studies have suggeste d that intracellular IL-1alpha, as well as exogenous IL-1alpha and IL- 1beta, can inhibit cell proliferation. Our results therefore implicate IL-1alpha, produced by epithelial cells in response to TCT, as a pote ntial intracellular mediator of the primary respiratory cytopathology of pertussis.