IL-6 signaling pathway differentiation for endometriosis and inflammatory diseases

Interleukin-6 (IL-6) plays a critical role in the pathogenesis of various chronic inflammatory diseases, tracked across numerous fields of research. Despite this, a crucial aspect often overlooked in studies is the differentiation between IL-6 classic-signaling and trans-signaling, leading to potential confounding of their findings; less than half of selected IL-6 studies included differentiation. This review delves into the distinction between IL-6 classic- and trans-signaling and their role in chronic inflammatory diseases and endometriosis. The unique pro-inflammatory nature of IL-6 trans-signaling, contrasted with the anti-inflammatory character of IL-6 classic-signaling, presents significant implications for research methodology, particularly in studies investigating anti-inflammatory interventions or interleukin inhibitors. Diagnostic failure to account for these distinct pathways may inadvertently misrepresent beneficial immune responses or the efficacy of interventions, posing significant challenges in predicting health outcomes. Interventions that do not differentiate these pathways could face reduced efficacy or safety. This review proposes adjustments to research methodologies and stresses the importance of careful interpretation of inflammatory markers in IL-6-related research. Examples of differentiation issues are discussed across the topics of endometriosis and multiple inflammatory diseases. By addressing this methodological issue, researchers could potentially improve patient outcomes, enhance the efficacy of interventions, and contribute to public health advancements.