Detection of cytokines at the site of tuberculin-induced delayed-type hypersensitivity in man

Cytokines are chiefly local mediators which play an important role in the regulation of the cell-cell interactions which may be involved in the development of the delayed-type hypersensitivity (DTH) reaction. Using immunohistochemical techniques, the presence of IL-1α, IL-Iβ, IL-6, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) in the skin in tuberculin-purified protein derivative (PPD)-induced DTH reactions was investigated in six normal individuals. Cells staining for these cytokines were first observed 6 h after PPD challenge, and they were detected throughout the duration of the 7-day experiment. The number of cells staining for IFN-γ reached a peak at 48 h, where 33% of the total aggregate cells were positive, but declined thereafter to 3% at day 7. On the other hand the number of cells staining for TNF-α and IL-1 persisted at high levels throughout the observation period of 7 days (e.g. at 48 h and thereafter, about 40% cells positive for TNF-α and 20% for IL-1α and IL-1β). Double immunofluorescence and staining on sequential sections showed that IFN-γ-staining cells were CD3⁺ T cells; TNF-α, IL-1 and IL-6 staining cells were mainly of the CD68⁺ macrophages/monocytes and that 80% of the CD1a⁺ cells (Langerhans-like cells) in the dermis contained TNF-α and IL-1. The presence of these cytokines at the site of inflammation suggests that they may be locally produced by the inflammatory cells. Their persistence during the reaction suggests that they are intimately associated with this response, and are involved in the development of the reaction.