Mycobacterial cell wall components induce the production of TNF-α, IL-1, and IL-6 by bovine monocytes and the murine macrophage cell line RAW 264.7

Johne's disease is characterized by a chronic enteritis that results in granulomatous inflammation, cachexia, and eventual death of cattle infected with Mycobacterium paratuberculosis. The cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6) have been associated with granuloma formation and wasting in other disease syndromes. The potential role of these cytokines in the development and progression of Johne's disease has not been investigated. Freshly isolated bovine peripheral blood monocytes and the murine macrophage cell line RAW 264.7 were examined for their ability to release inflammatory cytokines in response to mycobacterial cell wall components. Bovine monocytes and RAW 264.7 cells incubated with M. paratuberculosis lipoarabinomannan (LAM), muramyl dipeptide (MDP), or lipopolysaccharide (LPS) released TNF-alpha, IL-1 beta, and IL-6 as detected by appropriate bioassays. Using the RAW 264.7 cells, cytokine mRNA levels were elevated after in vitro incubation with live M. paratuberculosis or LPS as determined using a reverse-transcriptase polymerase chain reaction procedure.