Upregulation of transforming growth factor-beta and interleukin-10 in cows with clinical Johne's disease.

Johne's disease progresses through distinct stages including a protracted subclinical stage in which the infection appears to be controlled; followed by a more acute stage in which the host animal demonstrates clinical signs such as diarrhea and weight loss. Little is known about the dynamics of the host immune response during these two phases of disease, however, it is possible that immune modulation in the early stages of disease may play an important role in disease progression. We hypothesized that the clinical stage of Johne's disease is mediated by the expression of cytokines such as transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) that may be accompanied by the downregulation of IFN-gamma gene expression. In the present study, tissue samples were collected from the ileum, ileocecal junction, ileocecal lymph node, and mesenteric lymph nodes of healthy, subclinically or clinically infected cows. The expression of TGF-beta, IL-10, and IFN-gamma genes in these tissues was determined by quantitative competitive RT-PCR. The results demonstrate that TGF-beta and IL-10 mRNA levels are higher in cows that have progressed to the clinical stage of disease compared to subclinically infected or healthy cows. In contrast, IFN-gamma gene expression was significantly higher in subclinically infected cows. These results suggest that a change in the balance of cytokines at the site of infection may contribute to the ability of the host to control Mycobacterium avium subsp. paratuberculosis infection. Copyright 2004 Elsevier B.V.