The meteorology of cytokine storms, and the clinical usefulness of this knowledge

Abstract

The term cytokine storm has become a popular descriptor of the dramatic harmful consequences of the rapid release of polypeptide mediators, or cytokines, that generate inflammatory responses. This occurs throughout the body in both non-infectious and infectious disease states, including the central nervous system. In infectious disease it has become a useful concept through which to appreciate that most infectious disease is not caused directly by a pathogen, but by an overexuberant innate immune response by the host to its presence. It is less widely known that in addition to these roles in disease pathogenesis these same cytokines are also the basis of innate immunity, and in lower concentrations have many essential physiological roles. Here we update this field, including what can be learned through the history of how these interlinking three aspects of biology and disease came to be appreciated. We argue that understanding cytokine storms in their various degrees of acuteness, severity and persistence is essential in order to grasp the pathophysiology of many diseases, and thus the basis of newer therapeutic approaches to treating them. This particularly applies to the neurodegenerative diseases.

COVID‐19 and seizures: Is there a link?

“…These polypeptides, also known as cytokines, can cross the blood-brain barrier, causing neuroinflammation, which can contribute to development of poststroke syndrome, encephalopathies, and chronic neurodegenerative diseases. 61 Evidence for a cytokine storm has also been reported in subgroups of patients with severe COVID-19. 42,62,63 Thus, cytokine storm must be considered as another possible cause of neuronal damage in patients with a severe COVID-19 disease course.…”

Cytokine storms in infectious diseases

“…Thus, cytokines and chemokines play a vital role in maintaining a healthy state through efficient control of invading microbes. Clark and Vissel review the history of cytokine storm and highlight the roles cytokines play in instructing proper immune responses as well as mediating determinantal immunopathology [4]. The primary focus is on the role of two historical soluble mediators, Tumor necrosis factor-α (TNF-α) and Interleuken-1 (IL-1), in multiple acute and chronic disease states.…”

Preterm Life in Sterile Conditions: A Study on Preterm, Germ-Free Piglets

“…The local ileal and systemic HMGB1 values were indeed higher (but statistically non-significantly) in the preterm group (Figure S2 in Supplementary Material), but all levels of transcription for HMGB1 receptors (RAGE, TLR2, TLR4, and TLR9) were unexpectedly lower in these piglets, and we were unable to elucidate the reason for the exception in the case for TLR4 levels in the colon. We suppose that this incongruity with our expected outcome would be clarified by the detection of soluble decoy receptors that can disrupt receptor triggering to prevent overactivation or dysregulation of the innate immunity ( 58 , 59 ).…”

“…Cytokines regulate many biological processes, including pregnancy, inflammation, and sepsis ( 55 , 62 ). While low and intermediate cytokine levels fulfill their physiological functions, high levels manifest as a “cytokine storm,” resulting in an excessive innate immune response that is harmful to the host ( 59 ). We speculate that in the case of the preterm group, intestinal underdevelopment may increase the release of inflammatory cytokines, but in levels appropriate for the physiological role of cytokines.…”