ELISA kits based on monoclonal antibodies do not measure total IL-1 beta synthesis

The paper by Herzyk et al. which appears in this issue of the Journal of Immunological Methods is an important and long overdue contribution. The study clearly and convincingly demonstrates that two widely used commercial ELISA kits fail to detect over 90% of the 31 kDa human IL-1 beta precursor (pro-IL-1 beta) in various cells. This is due to the specificity of the monoclonal antibodies raised to the mature 17 kDa IL-1 beta and used in the commercial kits (or in 'home made' ELISAs). The significant amount of pro-IL-1 beta which is not measured by the kits casts doubt on the accuracy of total IL-1 beta synthesis reported in hundreds of published studies. Investigators evaluating cellular synthesis of IL-1 in the development of new drugs or IL-1 levels in health and disease increasingly rely on commercial detection kits. In this commentary, the importance and methods for determining total IL-1 beta synthesis are reviewed. In view of the preliminary positive results reported on the success of the IL-1 receptor antagonist (IL-1ra) in clinical trials, attention should be focused on the amount of IL-1 produced in disease and on the balance of IL-1 versus IL-1ra synthesis. Thus, continued use of these ELISA kits which do not detect pro-IL-1 beta will confound the interpretation of the IL-1 beta determinations.