Inflammatory protease
Caspase-1/IL-1β activation↓
Also searched as Caspase-1/IL-1β activation.
Blocking this step makes the heart pump better and leak fewer damage markers — which is the difference between a marker that tracks a disease and a step that causes it. It rises within the first week of infection.
In depth
The enzyme that activates the alarm cytokine and triggers inflammatory cell death.
What drives it
Inflammatory alarm increases it.
PMID 32328491 — this one was confirmed in actual human hearts, not only in mice. 'The presence of the NLRP3 inflammasome has been shown in endomyocardial biopsies of patients with acute myocarditis' (ScienceDirect Topics — Coxsackievirus B3 overview (citing Toldo et al. 2014; Wang, Gao & Xiong 2014; Wang et al. 2018)). Most of what is known about this illness comes from animals — this step was found in tissue taken from living patients. And the chain is timed: 'Infection with coxsackievirus B3... is associated with enhanced NLRP3 activation together with increased ASC, caspase-1 and IL-1β expression observed within 7 days from the infection in mice.'. PMID 32328491
The Handbrake the Virus Releases reduces it.
And this is the cruellest trick in the whole MAP: the virus releases the brake on the cell's self-destruct. 'both 2A and 3C are required for cleavage of CARD8, which normally functions to inhibit activation of CASP1 and pyroptosis' (pmc10178405 · PMID 37175422 — Role of Coxsackievirus b3-Induced Immune Responses in the Transition from Myocarditis to Dilated Cardiomyopathy and Heart Failure). ⇒ CARD8 is a handbrake. Cutting it lets the inflammatory cell-death machinery run. the bursting cell death is not an accident of the infection — the virus actively unlocks it. PMID 37175422
What it drives
It increases Inflammation signal (IL-1β).
10.3389/fimmu.2023.1128358 — this one was confirmed in actual human hearts, not only in mice. 'The presence of the NLRP3 inflammasome has been shown in endomyocardial biopsies of patients with acute myocarditis' (ScienceDirect Topics — Coxsackievirus B3 overview (citing Toldo et al. 2014; Wang, Gao & Xiong 2014; Wang et al. 2018)). Most of what is known about this illness comes from animals — this step was found in tissue taken from living patients. And the chain is timed: 'Infection with coxsackievirus B3... is associated with enhanced NLRP3 activation together with increased ASC, caspase-1 and IL-1β expression observed within 7 days from the infection in mice.'. doi 10.3389/fimmu.2023.1128358
It increases Inflammatory cell rupture.
PMC6505044 — A different kind of dying. Ordinary programmed cell death is quiet and tidy — the cell folds itself away. This one bursts, spilling its contents and inflaming everything around it. And the trigger is named: 'in experimental CVB3-induced myocarditis, inflammasome activation and subsequent pyroptosis seem to be mediated by cathepsin B' (ScienceDirect Topics — Coxsackievirus B3 overview (citing Toldo et al. 2014; Wang, Gao & Xiong 2014; Wang et al. 2018)). ⇒ that is why this illness amplifies itself: every cell that dies this way recruits more inflammation to kill the next one. PMC6505044
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.