Experimental silicosis: a shift to a preferential IFN-gamma-based Th1 response in thoracic lymph nodes

In chronic silicosis, mechanisms leading to lymphocyte activation are still poorly understood, although it is well known that not only the lung but al so the draining lymph nodes are affected. In the present study, we investig ated T-cell activation by analysis of cytokine expression in the enlarged t horacic lymph nodes of rats 2 mo after an 8-day silica aerosol exposure. In the case of helper T cell (Th) type 1 cytokines, we found a significant in crease in interferon (IFN)-gamma mRNA expression, whereas interleukin (IL)- 2 expression remained unchanged. In contrast, gene transcription for the Th 2-type cytokines IL-4 and IL-10 was diminished. In addition, with use of an in vitro lymphocyte-macrophage coculture system, an enhanced IFN-gamma and a reduced IL-10 release were shown with cells from silicotic animals. With regard to IFN-gamma-inducing cytokines, we observed enhanced IL-12 mRNA le vels in vivo, whereas IL-18 gene expression was slightly decreased. These d ata indicate that a persistent shift toward an IFN-gamma-dominated type 1 ( Th1/cytotoxic T cell type 1) T-cell reaction pattern occurred within the th oracic lymph nodes of silicotic animals. Thus a mutual activation of lympho cytes and macrophages may maintain the chronic inflammatory changes that ch aracterize silicosis.