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 responsible for destruction of ciliated epithelial cells lining the large airways. In vitro, TCT has been shown to cause this specific pathology in human or hamster respiratory epithelium and to inhibit the proliferation of cultured hamster trachea epithelial cells. The diverse biological actions of muramyl peptides, including adjuvanticity, somnogenicity, and 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 hamster trachea epithelial cells and reproduced the pathology of TCT in hamster tracheal organ culture. Tumor necrosis factor alpha and IL-6, cytokines also associated with inflammation, were unable to reproduce TCT cytopathology. Furthermore, exposure of respiratory epithelial cells to TCT stimulated production of cell-associated IL-1 alpha, which could be detected within 2 h of TCT treatment. In contrast, there was no evidence of TCT-triggered release of IL-1. Previous studies have suggested that intracellular IL-1 alpha, as well as exogenous IL-1 alpha and IL-1 beta, can inhibit cell proliferation. Our results therefore implicate IL-1 alpha, produced by epithelial cells in response to TCT, as a potential intracellular mediator of the primary respiratory cytopathology of pertussis.
Heiss
L N
LN
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110.
Moser
S A
SA
Unanue
E R
ER
Goldman
W E
WE
D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003603:Cytotoxins / Q000633:toxicity*; D004848:Epithelium / Q000187:drug effects; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000633:toxicity; D015850:Interleukin-6 / Q000633:toxicity; D008647:Mesocricetus; D010457:Peptidoglycan / Q000633:toxicity*; D014132:Trachea / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity; D010566:Virulence Factors, Bordetella / Q000633:toxicity*
D003603:Cytotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D010457:Peptidoglycan; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; C059708:tracheal cytotoxin, Bordetella pertussis