 Severe inflammation can cause the HPA axis to malfunction, resulting in decreased production of anti-inflammatory glucocorticoids from the adrenal cortex. This leads to a decrease in responsiveness to ACTH, which is further exacerbated by the presence of Illinois 1-beta. Illinois 1-beta causes DNMT1 to increase its activity on the SDHB gene, resulting in lowered levels of SDHB protein and thus reduced succinate levels. Succinate accumulates due to this reduction in SDHB, which then impairs oxidative phosphorylation and ATP synthesis, as well as increases reactive oxygen species, RS. These factors all contribute to decreased steroidogenesis, ultimately leading to decreased production of anti-inflammatory glucocorticoids. This article was authored by Ivona Metska, Anquit, Iman Haq, and others.