Modulation of the cytokine responses in equine macrophages following TACE-inhibition.

The detrimental effects of the pro-inflammatory cytokine TNF-alpha during equine acute abdominal disease are well known. Its pivotal role in many human diseases has led to various in-depth studies regarding its release mechanism, in particular by TNF-alpha converting enzyme (TACE). In this study we investigated the inhibitory effect of a TACE-inhibitor on cytokine release (TNF-alpha, IL-1alpha and IL-6) in three different cell models, including U937 cells, a recently established equine macrophage cell line, known as eCAS, and primary equine PBMC. The aim was to show the similarity of TNF-alpha release through the TACE mechanism in human and equine cells after stimulation with LPS. Results indicate that, by using a TACE-inhibitor, TNF-alpha, IL-1alpha and IL-6 release can be reduced in both equine cell models and achieved comparable results in the human U937 cells. These results suggest that equine TNF-alpha, like its human homologue, is released from its membrane-bound position by TACE.