By adoptive transfer assays, we found that mice receiving NLRP3 up-regulated macrophages showed much more abundant cardiac IL-1β production and more severe myocardial inflammation, while those receiving NLRP3 down-regulated macrophages showed much less IL-1β production and milder myocarditis, indicating that NLRP3 up-regulated macrophages played a pathological role in CVB3-induced myocarditis.
Our data revealed that (1) the P-AKT2/SPK1 (P-SPK1) and P-MEK/P-ERK signaling cascades acted separately in the regulation of macrophage migration; (2) P-AKT2/SPK1 (P-SPK1) played a relatively important role compared to P-MEK/P-ERK cell signaling in LPS-induced macrophage migration; (3) atorvastatin (ATV) inhibited macrophage migration by inhibiting P-AKT2/SPK1 (P-SPK1) cell signaling, but ATV could increase P-MEK and P-ERK protein expression; (4) ATV has a beneficial effect on LPS-induced myocarditis via inhibition of P-AKT2/SPK1-mediated macrophage recruitment, apoptosis, TNFα, IL-1β, and IL-6; (5) ATV-offered protection against LPS-induced myocarditis was eliminated from SPK1-KO mice; (6) SPK1 may play a harmful role in LPS-induced myocarditis.
Interestingly, interfering with IL-1 has proved to be also effective in other cardiovascular manifestations, such as myocarditis, arrhythmias, and heart failure.
Both IL-1α and IL-1β have been shown to induce myocarditis and aneurysm formation in <i>Lactobacillus casei</i> cell-wall extract mouse model of KD; both being successfully improved with IL-1 blockade treatment such as anakinra.
Using reverse transcriptase polymerase chain reaction (RT-PCR), we examined the expression of interleukin 1 beta (IL-1 beta), IL-6, IL-8 and tumour necrosis factor alpha (TNF-alpha) and the presence of enteroviral genomic RNA in endomyocardial biopsy tissues obtained from patients with myocarditis and DCM.