The Biphasic Immune Pattern of Sepsis: From Pathophysiological Mechanisms to Precision Immunotherapy and Future Challenges

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, characterized by a complex biphasic immune pattern. Contemporary perspectives emphasize that during the early stages of sepsis, excessive inflammatory responses and emerging immunosuppression coexist rather than occur sequentially. This review systematically elucidates the pathophysiological basis of this early coexisting biphasic immune pattern in sepsis, providing an in-depth analysis of the key mechanisms underlying the initial cytokine storm and the subsequent development of immune paralysis. Furthermore, it highlights precision immunotherapeutic strategies tailored to distinct immune phenotypes, encompassing immune modulation and immune stimulation approaches. The review also critically examines the major challenges in clinical translation and explores future directions in the field. By integrating current knowledge on the immunopathology of sepsis, this article aims to offer a comprehensive theoretical framework to advance the understanding of sepsis immune dysregulation and to foster the development of novel targeted therapies.