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Interleukin-1β (IL-1β) is activated by inflammasome-associated caspase-1 in rare autoinflammatory conditions and in a variety of other inflammatory diseases. Therefore, IL-1β activity must be fine-tuned to enable anti-microbial responses whilst limiting collateral damage. Here, we show that precursor IL-1β is rapidly turned over by the proteasome and this correlates with its decoration by K11-linked, K63-linked and K48-linked ubiquitin chains. The ubiquitylation of IL-1β is not just a degradation signal triggered by inflammasome priming and activating stimuli, but also limits IL-1β cleavage by caspase-1. IL-1β K133 is modified by ubiquitin and forms a salt bridge with IL-1β D129. Loss of IL-1β K133 ubiquitylation, or disruption of the K133:D129 electrostatic interaction, stabilizes IL-1β. Accordingly, Il1bK133R/K133R mice have increased levels of precursor IL-1β upon inflammasome priming and increased production of bioactive IL-1β, both in vitro and in response to LPS injection. These findings identify mechanisms that can limit IL-1β activity and safeguard against damaging inflammation.

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Purpose: Platelet count, mean platelet volume, platelet distribution width, and plateletcrit are standard indices of platelet activation that have been studied in retinal vein occlusion (RVO) and its subtypes: branch retinal vein occlusion and central retinal vein occlusion. This systematic review and meta-analysis aimed to assess the association between these platelet parameters and RVO. Methods: We searched for studies investigating the association between these platelet indices and RVO in multiple online databases from inception to August 2020. Mean differences and the associated confidence intervals were obtained and calculated for each included study and pooled using random-effects inverse variance modeling. Meta-regression was used to explore interstudy and intrastudy heterogeneity. Results: Thousand three hundred and twenty-five unique studies were screened, from which 24 studies encompassing 2,718 patients were included. Mean platelet volume and platelet distribution width were significantly elevated in RVO, with pooled mean differences of 0.45 fL (95% CI 0.24–0.66, P < 0.0001) and 1.43% (95% CI 0.57–2.29, P = 0.0011), respectively. Platelet count and plateletcrit were not significantly associated with RVO. Mean platelet volume was also independently elevated in branch retinal vein occlusion and central retinal vein occlusion. Conclusion: Mean platelet volume and platelet distribution width are significantly elevated in RVO. Further research is required to explore the independence and potential prognostic significance of these associations.

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The neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) are emerging haematological inflammatory biomarkers. However, their significance in retinal vein occlusion (RVO) and its subtypes, branch and central RVO (BRVO and CRVO, respectively), is uncertain. This systematic review and meta‐analysis aimed to clarify the association of NLR and PLR with RVO. We searched MEDLINE (Ovid), EMBASE (Ovid) and the Cochrane Library for studies investigating the association of NLR and PLR with RVO from inception to 2 December 2020. We used random‐effects inverse‐variance modelling to generate pooled effect measures. We used bivariate Bayesian modelling to meta‐analyse the ability of NLR and PLR to differ between individuals with and without RVO and performed meta‐regression and sensitivity analyses to explore inter‐study heterogeneity. Eight studies published encompassing 1059 patients were included for analysis. Both NLR and PLR were significantly elevated in RVO, with pooled mean differences of 0.63 (95% confidence interval (CI) 0.31–0.95) and 21.49 (95% CI 10.03–32.95), respectively. The pooled sensitivity, specificity and area under the Bayesian summary receiver operating characteristic curve were, respectively, 0.629 (95% credible interval (CrI) 0.284–0.872), 0.731 (95% CrI 0.373–0.934) and 0.688 (95% CrI 0.358–0.872) for NLR; and 0.645 (95% CrI 0.456–0.779), 0.616 (95% CrI 0.428–0.761) and 0.621 (95% CrI 0.452–0.741) for PLR. Mean and variability of age and diabetes mellitus prevalence partially explained between‐study heterogeneity. NLR and PLR are significantly elevated in RVO. Future research is needed to investigate the potential prognostic value and independence of these findings.

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