Yusho patients show increased serum IL-17, IL-23, IL-1β, and TNFα levels more than 40 years after accidental polychlorinated biphenyl poisoning

The Yusho poisoning incident, caused by rice oil contaminated with polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs), and polychlorinated dibenzofurans (PCDFs) generated by heat-denatured PCBs, occurred in 1968 in western Japan. Although severe symptoms are rarely observed today, the levels of PCBs and PCDFs in the sera of Yusho patients remain high. The aryl hydrocarbon receptor (AhR), which also acts as a dioxin receptor, is a transcriptional regulator that mediates dioxin toxicity. Recent studies show that dioxin mediates its immune toxic effects via AhR and that AhR activation induces dysregulation of interleukin (IL)-17-producing T (T(H)17) cells. This study therefore hypothesized that Yusho patients would show dysregulated T(H)17 cell-mediated immune responses. To validate the hypothesis, levels of IL-17 and IL-22, each secreted by T(H)17 cells, along with IL-1 beta and IL-23 were measured in serum samples from 40 Yusho patients and 40 age-matched controls. Levels of tumor necrosis factor (TNF)-alpha potentially secreted by T(H)17 cell-stimulated neutrophils and macrophages were also measured. The results indicated that serum IL-17 levels, as well as those of IL-1 beta, IL-23, and TNF alpha, were significantly higher in Yusho patients than in controls. In contrast, serum IL-22 levels were significantly lower in the Yusho patients. These results suggest that Yusho patients have dysregulated T(H)17 cell-mediated immune responses that may be linked to inflammation.