Circulating concentrations of CRP, PCT, interleukin (IL)-10 and IL-1 receptor antagonist (IL-1Ra) were significantly higher in patients with sepsis, with IL-10 identified as the best biomarker in differentiating sepsis from SIRS.
Lethality from sepsis is believed to be mediated by a proinflammatory cytokine cascade, yet blocking the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) fails to prevent mortality in human disease and a mouse model of sepsis induced by cecal ligation and puncture (CLP).
We found that the transcription levels of interleukin 1 (IL-1) and interleukin 6 (IL-6) mRNA in TECs increased significantly during sepsis and these processes can be blocked by splenectomy.
Several serum-based biomarkers such as C-reactive protein, lactate, presepsin, and cytokines, such as interleukin-1 (IL-1), and IL-6 have been evaluated as early indicators of sepsis but none have been proven sensitive and/or specific enough to make a definitive diagnosis.
Following its initial failures in the treatment of sepsis and the moderate success in the treatment of rheumatoid arthritis, IL-1 blocking therapies had a renaissance in the treatment of a number of autoinflammatory conditions, and IL-1 blocking therapies have been Food and Drug Administration (FDA)-approved for the treatment of the autoinflammatory conditions: cryopyrin-associated periodic syndromes (CAPS).
The IL-1 receptor-associated kinase (IRAK-1) plays a central role in TLR2- and TLR4-induced activation of nuclear factor (NF)-kappaB, a critical event in the transcriptional regulation of many sepsis-associated proinflammatory mediators.
In this study, two polymorphisms (IL-1β (-511) and IL-1R) were significantly associated with the development of MOF and mortality, where as IL-1α (-889) polymorphism associated with susceptibility for sepsis.
Thrombin-cleaved IL-1α was detected in humans during sepsis, pointing to the relevance of this pathway for normal physiology and the pathogenesis of inflammatory and thrombotic diseases.
The potential significance of IL-1 members in sepsis will also be explored, together with the clinical implications for treating this dangerous condition.
The physiological significance of the tolerance to endotoxin and increased expression of IL-1R2 on sepsis PMN is unknown, but may represent an attempt by the host to protect itself from the deleterious effects of disseminated inflammation.
Bezafibrate treatment led to a reduction in leukocyte adherence, improved functional capillary density (FCD), and a reduction in interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α) and granulocyte macrophage colony stimulating factors (GM-CSF) plasma levels in experimental sepsis.