Involvement of Propionibacterium acnes in the Augmentation of Lipogenesis in Hamster Sebaceous Glands In Vivo and In Vitro

Propionibacterium acnes is considered to be involved in the aggravation of acne vulgaris, but it remains unclear whether P. acnes directly influences lipogenesis in sebaceous glands. In this study, we showed that a culture medium of P. acnes (acnes-CM) and formalin-killed P. acnes (F-acnes) prepared from P. acnes strains, JCM6473 and JCM6425, intracellularly augmented lipid droplet formation and triacylglycerol (TG) synthesis in undifferentiated and insulin-differentiated hamster sebocytes. Acnes-CM and F-acnes prepared from four clinical P. acnes strains elicited the same lipogenesis augmentation. The augmented TG production resulted from an increase in the diacylglycerol acyltransferase activity. Topical application of acnes-CM to the skin of hamster auricles every day for 4 weeks revealed that sebum accumulation was augmented in sebaceous glands and ducts. Furthermore, both acnes-CM and F-acnes increased the production of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a cytochrome P450 (CYP)-linked sebaceous lipogenic factor, in differentiated sebocytes. A CYP inhibitor, SKF-525A, decreased the acnes-CM- and F-acnes-augmented production of TG and 15d-PGJ2. Thus, to our knowledge these results provide previously unreported evidence that P. acnes directly participates in the augmentation of sebaceous lipogenesis through a proposed mechanism in which an increase of 15d-PGJ2 production through the CYP pathway is closely associated with the enhancement of TG production

Initial intravenous immunoglobulin therapy without aspirin for acute Kawasaki disease: a retrospective cohort study with a Bayesian inference

Objective To clarify the necessity of acetylsalicylic acid (ASA) administration combined with intravenous immunoglobulin (IVIG) therapy in the treatment of acute Kawasaki disease.Design Retrospective cohort study.Setting Multicentre.Participants This study included 735 patients with Kawasaki disease aged ≤10 years and hospitalised between 4 and 10 days of illness in eight Japanese hospitals from January 2016 to December 2020.Exposures High-dose (HD) ASA was administered with initial IVIG to 333 patients in 6 hospitals (HD group). ASA was not administered routinely to 402 patients in the other two hospitals, and low-dose ASA was only administered when patients developed coronary artery lesions or pericardial effusion (non-HD group).Primary and secondary outcome measures The primary outcome was the presence of coronary artery lesions, defined as a coronary artery diameter >+2.5 SD of body surface area within 1 month of onset. The secondary outcome was responsiveness to the initial IVIG therapy. Adjusted risk ratios for the outcomes were calculated using modified Poisson regression models. Bayesian analysis was conducted to estimate the posterior probability of the treatment effect of HD ASA under several prior distributions.Results The incidence of coronary artery lesions was not significantly higher in the HD group than in the non-HD group (12/333 (3.6%) vs 15/402 (4.0%)). The proportion of non-responders to initial IVIG was similar between the two groups (HD group: 78/333 (23%); non-HD group: 83/402 (22%)). In the Bayesian analysis, considering a difference of ≤2% to be of no clinical importance, there was only a 9.3% chance of reduced risk of coronary artery lesions in the HD group compared with the non-HD group even with a strongly enthusiastic prior for HD treatment.Conclusions Compared with HD ASA treatment, treatment without ASA in the acute phase of Kawasaki disease was not associated with increased complications from Kawasaki disease