Cytokine Storm

Description

Cytokine storm, synonymous with “Cytokine Release Syndrome” (CRS) and “secondary haemophagocytic lymphohistiocytosis” (sHLH), is a severe and sudden hyper-inflammatory condition that can lead to multi-organ failure and death.  This life-threatening condition is characterized by over-stimulated immune cells that produce highly elevated levels of various inflammatory mediators called cytokines (hypercytokinemia). With both pro-inflammatory cytokines (such as TNF-α, IL-1, and IL-6) and anti-inflammatory cytokines (such as IL-10, and IL-1Ra) becoming elevated in the blood, a turbulent and often lethal interplay between these cytokines escalates into a “Cytokine Storm”.

In the absence of a prompt diagnosis and subsequent medical intervention to stop the cytokine storm, the lungs can develop acute respiratory distress syndrome (ARDS) and (along with other organs) suffer permanent damage. Because of this, it is absolutely critical to gain a quick and comprehensive testing of the patient’s immune system.

HLH Cytokine Storm Causes:

Most commonly, a cytokine storm is triggered by viral infections, but can also be caused by other immune-system triggering events such as a bacterial infection (sepsis), fungal infection, an autoimmune disease such as multiple sclerosis or SLE, and possibly an adverse reaction to a drug (i.e.. cancer therapy) / vaccination (infusion reaction) and pollution.  Macrophage activation syndrome (MAS) (a variation of HLH) is seen in some rheumatic diseases such as juvenile idiopathic arthritis, adult onset Still’s and systemic lupus erythematous (SLE).

Typical Increased Cytokines and Other Biomarkers seen in Cytokine Storm: 

EGF, IL-1β, IL-1ra, IL-2, IL-6, IL-10, IL-7, IL-8, G-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, TNFα, sIL-2Rα (sCD25).

Most notably are IL-6 and TNFα.

Other elevated biomarkers include serum ferritin, high C-reactive protein (CRP), D-dimer, lactic dehydrogenase (LDH), ALT/AST (liver dysfunction), and low blood counts (cytopenias).

HLH Cytokine Storm Treatments:

Anakinra – Recombinant and slightly modified version of the human interleukin 1 receptor antagonist protein

Tocilizumab – Anti-IL6 monoclonal antibody

Lenzilumab – Monoclonal antibody that targets GM-CSF which reduces activation of myeloid cells and decreasing the production of IL-1, IL-6, MCP-1, MIP-1, and IP-10.

Infliximab – TNF inhibitor via monoclonal antibody that targets TNFα

Adalimumab – TNF inhibitor via human antibody that targets TNFα