Ribeiro Ribeiro, AL; (2018) Effects of sodium benzoate on the innate immune response to gram-negative bacteria and Toll-like receptor stimulation. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Sodium benzoate (NaB) is a sodium salt that is widely used in the pharmaceutical, cosmetic and food industries. This widespread use results in almost everybody in the world being exposed daily to this compound. Currently very little is known about the effects of NaB can have on the immune response, even though it has been associated with the clinical course of chronic inflammatory diseases, such as orofacial granulomatosis and neurodegenerative disorders. Here, I show that THP-1 cells, a monocytic human cell line presents an altered immune response when exposed to NaB. Immunologically stimulated THP-1 cells in the presence of NaB secreted reduced levels of IL6 and IL1β and higher levels of TNF, while other cytokines such as IP10 and IL8 were unaffected. The inhibitory effect in IL6 and IL1β secretion was a consequence of a free radical scavenging characteristic of NaB, which neutralizes the reactive oxygen species (ROS) generated downstream of TLR activation. This resulted in the impairment of a secondary signalling event, which is required to fully activate the cells immune response. The use of microarray analysis in combination with q quantitative proteomic analysis revealed that NaB has a significant effect on the THP-1 cells beyond the alteration in cytokine secretion. NaB also interferes with cellular amino acid metabolism and has a major attenuating effect on the immune response. Taken together, these results suggest that NaB is not inert and has a major effect on a cells ability to mount an immune response. These findings could have major implications in how NaB is used in the future and in particular if it can be beneficial as a treatment for chronic inflammatory diseases, such as diabetes, atherosclerosis, rheumatoid arthritis, neurodegenerative disorders, and so on. On the other hand, by disturbing the inflammatory response, NaB could have a negative impact on other conditions such as orofacial granulomatosis. Further work will be needed to determine the role NaB plays in human inflammatory diseases.

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