Interleukin-1 beta and Interleukin-6 signaling (IL-1β/IL-6 signaling)

The Interleukin-1 beta (IL-1β) and Interleukin-6 (IL-6) signaling pathways are critical mediators of the innate immune response and are central drivers of systemic and local inflammation [2, 15]. IL-1β is a potent pro-inflammatory cytokine primarily produced via NLRP3 inflammasome activation, while IL-6 is a pleiotropic cytokine that regulates the acute-phase response and immune cell differentiation through classic and trans-signaling mechanisms [16, 19]. These pathways often act in a coordinated or synergistic manner; for instance, IL-1β can induce the expression of IL-6, and both converge on downstream transcription factors like NF-κB and STAT3 to promote inflammatory gene expression [6, 12]. Dysregulation of this dual signaling axis is implicated in a wide range of pathologies, including rheumatoid arthritis, cardiovascular disease, neuroinflammation, and cytokine release syndrome [14, 15, 18]. Therapeutic strategies include the use of monoclonal antibodies to neutralize the cytokines (e.g., canakinumab, siltuximab), competitive receptor antagonists (e.g., anakinra, tocilizumab), or small molecule inhibitors targeting downstream kinases like Janus kinases (JAKs) [7, 17]. Combined blockade of both IL-1β and IL-6 signaling is an emerging strategy to manage severe inflammatory states, such as cytokine storms, where single-target inhibition may be insufficient [2, 9].

Other names

IL-1/IL-6 axisInterleukin-1 and Interleukin-6 signalingPro-inflammatory cytokine signalingIL-1 and IL-6 pathways

Inhibition of IL-1β or IL-6 signaling through cytokine neutralization, competitive receptor antagonism, or inhibition of downstream signal transduction (e.g., JAK/STAT pathway).