The plasma data for RRMS patients, indicating a reduced capacity of macrophages to synthesise 25-HC, is in-line with the recent study by Reboldi et al. which shows that in mouse macrophages 25-HC is a mediator of negative feedback towards interleukin 1 (IL-1) family cytokine production and inflammasome activity, through binding to INSIG (insulin-induced gene) and antagonising the sterol response element-binding protein-2 (SREBP-2) driven mevalonate pathway, thereby, reducing Il1b transcription and repressing IL-1-activating inflammasomes [33]. The gene discussed is SREBF2; the disease is relapsing-remitting multiple sclerosis.