Effects of lauric acid on the production of pro-inflammatory mediators and its risk assessment

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Lauric acid (LA), a C-12 natural fatty acid, has recently been reported to induce the activity of a pivotal inflammatory transcription factor, NFkappaB, and one of its target genes, cyclooxygenase (COX-2), in macrophages. COX-2 is now recognized as a central player in the onset of inflammation and inflammation-associated carcinogenesis. However, its effects on pro-inflammatory cytokine production as well as in vivo risk assessment are yet to be determined. In the present study, we found that LA increased the production of IL (interleukin)-1beta, MIF (macrophage migration inhibitory factor), and IL-6, but not TNF (tumor necrosis factor)-alpha, in mouse peritoneal macrophages. In the mouse ear inflammation test, LA did not induce inflammation up to 1000-fold dose to TPA, which was used as a positive control, and also did not significantly up-regulate COX-2 mRNA expression. Then, LA was subjected to a short-term model for colon cancer, in which aberrant crypt foci (ACF) was employed as a histological tumor marker. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were used as the tumor initiator and promoter, respectively. Oral feeding of LA at a dose of 1% in the basal diet for 10 weeks tended to decrease body weight and colorectal length (a maker for colonic inflammation) and to increase liver weight as compared with positive control (AOM+DSS), suggesting the side-effect of LA. On the other hand, the formation of ACF, the weights of kidney and fatty tissues did not markedly changed between those groups. In conclusion, although LA was revealed, for the first time, to enhance some pro-inflammatory biomarkers both in vitro and in vivo, definitive evidence of harmful effects of LA remain to be identified, and thus further efforts for addressing those issues will be warranted in the near future.