On the possible inhibition of macrophage inflammatory responses by phytic acid produced by Echinococcus multilocularis

Echinococcus multilocularis, causing agent of alveolar echinococcosis, down-regulates host immunity 1,2. Salzmann et al showed that macrophages close to the parasite produce little IL-6 and the parasite extract mimics this inhibition in cultured macrophages 3. The authors then showed that E. multilocularis contains phytic acid and that commercial phytic acid inhibits cytokine responses in stimulated macrophages. Through comparison with effects of EDTA and intracellular calcium measurements, they concluded that phytic acid inhibits macrophage responses through calcium depletion, extrapolating this conclusion to assays with parasite extract and infection setting. However, the interaction between phytic acid and calcium is complex 4,5. Calcium is indeed depleted in the assays with commercial phytic acid according to our quantitative predictions. However additional changes occur including formation of solid calcium phytate, which probably moderates the inhibition of responses observed under calcium depletion. We calculate that in the experiments with parasite extract, phytic acid present cannot deplete calcium and therefore inhibition must be driven by a different mechanism, possibly independent of phytic acid. Further, we argue that calcium depletion is an unlikely in vivo immune regulatory mechanism. We propose that biological assays using calcium phytate are needed for ascertaining whether phytic acid has biologically relevant anti-inflammatory activity.