with the correlation of total IL-18 and macrophage activation syndrome (MAS)-prone conditions, they found elevated free IL-18 specifically in patients with Still's disease, and also observed a higher IL-18/IL-18BP affinity than previously described. Further investigation is warranted to better understand discrepancies between calculated and measured free IL-18, and appropriate caution should be taken in the interpretation of calculated free IL-18 until the aforementioned assumptions have been addressed. This report provides the first clinical clues that the association between free IL-18 and MAS is no mere epiphenomenon. Specifically, the magnitude and chronicity of elevated IL-18 in NLRC4-related MAS (and in most systemic juvenile idiopathic arthritis 5) might suggest a ''priming'' effect for exuberant MAS-like responses. However, this patient's rapid improvement also implicates a role for IL-18 in propagating inflammation. In addition, the patient's enterocolitis was associated with substantially more free IL-18 in stool than in serum, suggesting less buffering by IL-18BP at mucosal surfaces. Overall, the important work initiated nearly 2 decades ago in describing the endogenous regulation of IL-18 continues to undergo scientific, and now clinical, refinement as we better understand the homeostatic and pathogenic functions of this cytokine.