Effect of Tracheal LPS With and Without Dapsone on Ferret Activity and Weight
There was no measureable effect of LPS with or without dapsone treatment on ferret activity or appetite and no difference in weight over 9 days when comparing these two groups (Fig 8).
Intraepithelial Neutrophil Accumulation in LPS-Inflamed Ferret Trachea
To evaluate the in vivo effect of dapsone, we used topical LPS coated onto an ETT to recruit neutrophils and inflame the trachea of anesthetized and spontaneously breathing ferrets. Control ferrets intubated with an ETT coated with only a water-soluble jelly (used as the LPS vehicle in the other group) showed few epithelial neutrophils (< 3/150 mm). One ferret with an LPS-inflamed airway and treated with nebulized vehicle did not complete the study because of death on day 6, and this animal was excluded from further analysis. As shown in Figure 9A, LPS exposure induced marked neutrophil accumulation in the ferret tracheal epithelium. Dapsone treatment reduced intraepithelial neutrophil number (Fig 9B). Orally administered dapsone tended to inhibit neutrophil recruitment (P = .3) (Fig 9C), and nebulized dapsone significantly inhibited neutrophil accumulation (P < .05) (Fig 9D).
MCT on Excised Tracheal Segments
MCT was timed over a 3-mm segment. LPS dramatically decreased MCT to 1 to 3 mm/min (normal, ^ 7 mm/min). Oral dapsone increased MCT, but the increase was not significant (P = .09). However, aerosol dapsone preserved MCT at near-normal velocity (6 mm/min, P = .007) compared with LPS control as shown in Figure 10.
Discussion about
We have shown that dapsone inhibits IL-8 secretion from NHBE cells stimulated with LPS. Dapsone is used to treat dermatologic disorders, most notably those with neutrophil infiltrates. It has been postulated that dapsone impairs neutrophil chemotaxis and function at the sites of inflammation, apparently without increased risk of opportunistic infections. This is consistent with immunomodulation, but not immunosuppression.