This study aimed to investigate the expression and significance of serum procalcitonin (PCT), leukotriene B4 (LTB4), Serum amyloid A (SAA), and C-reactive protein (CRP) in children with different types of pneumonia caused by different pathogenic infections. One hundred and one children with pneumonia admitted to The Fifth People Hospital of Zhuhai from July 2019 to June 2020 were enrolled and divided into 38 cases in the bacterial group, 30 cases in the mycoplasma group, and 33 cases in the virus group according to the different types of pathogens. The patients were divided into 42 cases in the noncritical group, 33 cases in the critical group, and 26 cases in the very critical group according to the pediatric clinical illness score (PCIS), and 30 healthy children were selected as the control group during the same period. Comparison of serum PCT, SAA: bacterial group > mycoplasma group > viral group > control group with significant differences (P < .05). Receiver operator characteristic (ROC) analysis showed that the area under the curves (AUCs) of serum PCT, LTB4, SAA, and CRP for the diagnosis of bacterial pneumonia were 1.000, 0.531, 0.969, and 0.833, respectively, and the AUCs for the diagnosis of mycoplasma pneumonia were 0.653, 0.609, 0.547, and 0.652, respectively, and the AUCs for the diagnosis of viral pneumonia were 0.888, 0.570, 0.955, and 1.000, respectively. Comparison of serum PCT, LTB4, SAA: very critical group > critical group > noncritical group > control group, with significant differences (P < .05). Serum PCT, LTB4, and SAA were negatively correlated with PCIS score by Pearson analysis (P < .05). Serum PCT and SAA showed diagnostic value for bacterial pneumonia, and serum SAA and CRP showed diagnostic value for viral pneumonia; serum PCT, LTB4, and SAA correlate with severity of disease and show higher expression with worsening of the condition.

BACKGROUND: Prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) are eicosanoids involved in modulation of the antiviral immune response. Recent studies have identified increased levels of several eicosanoids in the plasma and bronchoalveolar lavage of patients with coronavirus disease (COVID-19). This study investigated correlations between plasma levels of PGE2 and LTB4 and clinical severity of COVID-19.
METHODS: This cross-sectional study involved non-infected (n = 10) individuals and COVID-19 patients classified as cured (n = 13), oligosymptomatic (n = 29), severe (n = 15) or deceased (n = 11). Levels of D-dimer a, known COVID-19 severity marker, PGE2 and LTB4 were measured by ELISAs and data were analysed with respect to viral load.
RESULTS: PGE2 plasma levels were decreased in COVID-19 patients compared to the non-infected group. Changes in PGE2 and LTB4 levels did not correlate with any particular clinical presentations of COVID-19. However, LTB4 was related to decreased SARS-CoV-2 burden in patients, suggesting that only LTB4 is associated with control of viral load.
CONCLUSIONS: Our data indicate that PGE2/LTB4 plasma levels are not associated with COVID-19 clinical severity. Hospitalized patients with COVID-19 are treated with corticosteroids, which may influence the observed eicosanoid imbalance. Additional analyses are required to fully understand the participation of PGE2 receptors in the pathophysiology of COVID-19.

The vast majority of coronavirus disease 2019 (COVID-19) disease occurs in outpatients where treatment is limited to antivirals for high-risk subgroups. Acebilustat, a leukotriene B4 inhibitor, has potential to reduce inflammation and symptom duration.
In a single-center trial spanning Delta and Omicron variants, outpatients were randomized to 100 mg/d of oral acebilustat or placebo for 28 days. Patients reported daily symptoms via electronic query through day 28 with phone follow-up on day 120 and collected nasal swab samples on days 1-10. The primary outcome was sustained symptom resolution to day 28. Secondary 28-day outcomes included time to first symptom resolution, area under the curve (AUC) for longitudinal daily symptom scores, duration of viral shedding through day 10, and symptoms on day 120.
Sixty participants were randomized to each study arm. At enrollment, the median duration was 4 days (interquartile range, 3-5 days), and the median number of symptoms was 9 (7-11). Most patients (90%) were vaccinated, with 73% having neutralizing antibodies. A minority of participants (44%; 35% in the acebilustat arm and 53% in placebo) had sustained symptom resolution at day 28 (hazard ratio, 0.6 [95% confidence interval, .34-1.04]; P = .07 favoring placebo). There was no difference in the mean AUC for symptom scores over 28 days (difference in mean AUC, 9.4 [95% confidence interval, -42.1 to 60.9]; P = .72). Acebilustat did not affect viral shedding or symptoms at day 120.
Sustained symptoms through day 28 were common in this low-risk population. Despite this, leukotriene B4 antagonism with acebilustat did not shorten symptom duration in outpatients with COVID-19. Clinical Trials Registration. NCT04662060.

In our previous study, intravenous (IV) injection of selenium alleviated breast cancer-related lymphedema (BCRL). This secondary analysis aimed to explore the metabolic effects of selenium on patients with BCRL. Serum samples of the selenium-treated (SE, n = 15) or the placebo-controlled (CTRL, n = 14) groups were analyzed by ultra-high-performance liquid chromatography with Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS). The SE group showed a lower ratio of extracellular water to segmental water (ECW/SW) in the affected arm to ECW/SW in the unaffected arm (arm ECW/SW ratio) than the CTRL group. Metabolomics analysis showed a valid classification at 2-weeks and 107 differential metabolites were identified. Among them, the levels of corticosterone, LTB4-DMA, and PGE3-which are known anti-inflammatory compounds-were elevated in the SE group. Pathway analysis demonstrated that lipid metabolism (glycerophospholipid metabolism, steroid hormone biosynthesis, or arachidonic acid metabolism), nucleotide metabolism (pyrimidine or purine metabolism), and vitamin metabolism (pantothenate and CoA biosynthesis, vitamin B6 metabolism, ascorbate and aldarate metabolism) were altered in the SE group compared to the CTRL group. In addition, xanthurenic acid levels were negatively associated with whole blood selenium level (WBSe) and positively associated with the arm ECW/SW. In conclusion, selenium IV injection improved the arm ECW/SW ratio and altered the serum metabolic profiles in patients with BCRL, and improved the anti-inflammatory process in lipid, nucleotide and vitamin pathways, which might alleviate the symptoms of BCRL.

To evaluate the safety and preliminary efficacy of topical rVA576, a dual inhibitor of complement component 5 (C5) and leukotriene B4 (LTB4), in patients with recalcitrant atopic keratoconjunctivitis (AKC) in the open label phase 1 TRACKER clinical trial.
Three patients diagnosed with moderate or severe AKC who had been on maximal topical treatment (antihistamines and ciclosporin) for at least three months prior to entry, and showed persistent symptoms and signs of inflammation, were recruited into the trial. Patients received rVA576 eye drops twice a day for 8 weeks. Patients were seen at baseline and weeks 1, 2, 4, 6 and 8. Safety data was recorded and a composite sum score of symptoms and signs was obtained. This score comprised symptoms such as itching, mucous discharge and photophobia, and conjunctival and corneal signs such as hyperemia, tarsal papillae, punctate keratitis and corneal neovascularization, all rated individually from 0 to 3 for a maximum score of 33.
Two of the three patients completed the initial open label phase of the trial. The third patient was unable to attend appointments and terminated the study early at day 14. Topical rVA576 was well tolerated with no serious adverse events reported. There was an average improvement in overall clinical score of 53%, composed of an improvement in symptoms of 65% [63.64-66.67%] and signs of 40% [40-40.12%] by day 56.
In this open label phase 1 TRACKER trial, rVA576 eye drops were well tolerated and showed a response across signs and symptoms of active inflammation. This study is exploratory but supports topical rVA576 safety and shows promising efficacy for recalcitrant AKC. A phase 2 randomised control trial is currently underway.

Sesquiterpene lactones (SL) are natural bioactive molecules indicated as potential scaffolds for anti-inflammatory and analgesic drug design. However, their anti-inflammatory applicability remains underestimated since the impact of SL on inflammatory nociception and tissue repair are overlooked. Thus, we used an integrated in silico, in vitro and in vivo framework to investigate the impact of tagitinin F (TAG-F) on lipopolysaccharide (LPS)-challenged macrophages, excisional skin wounds, and carrageenan-induced paw edema and mechanical hyperalgesia in mice. RAW 264.7 macrophages in culture were challenged with LPS and treated with TAG-F (5, 10, 50 and 100 μM). The paw of BALB/c mice was injected with carrageenan and treated with 0.5% and 1% TAG-F. Excisional wounds were also produced in BALB/c mice and treated with 0.5% and 1% TAG-F. Our results indicated a consistent concentration-dependent downregulation in 5-lipoxygenase, cyclooxygenase 1 and 2 (COX-1 and COX-2), matrix metalloproteinase 1 and 2 (MMP-1 and MMP-2) activities; as well as attenuation in prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and tumor necrosis factor-α (TNF-α) production in both in vitro and in vivo models. In vivo, TAG-F also attenuated carrageenan-induced paw edema and mechanical hyperalgesia in mice. From the excisional skin wound, TAG-F was still effective in reducing neutrophils and macrophages infiltration and stimulating collagen deposition in the scar tissue, accelerating tissue maturation. Together, our findings indicate that the anti-inflammatory effect of TAG-F is more comprehensive than previously suggested, exerting a significant impact on the control of edema, inflammatory pain and modulating central metabolic processes linked to skin wound healing.

Omega-3 polyunsaturated fatty acid (ω-3 PUFA) have been reported to have beneficial cardiovascular effects, but its mechanism of protection against acute myocardial infarction (AMI) who are under guideline-based therapy is not fully understood. Here, we used a metabolomic approach to systematically analyze the eicosanoid metabolites induced by ω-3 PUFA supplementation and investigated the underlying mechanisms.
Participants with AMI after successful percutaneous coronary intervention were randomized to 3 months of 2 g daily ω-3 PUFA and guideline-adjusted therapy (n = 30, ω-3 therapy) or guideline-adjusted therapy alone (n = 30, Usual therapy). Functional PUFA-derived eicosanoids in plasma were profiled by metabolomics. Clinical and laboratory tests were obtained before and 3 months after baseline and after the study therapy.
By intent-to-treat analysis, the content of 11-HDoHE, 20-HDoHE and 16,17-EDP and that of epoxyeicosatetraenoic acids (EEQs), derived from docosahexaenoic acid and eicosapentaenoic acid, respectively, were significantly higher with ω-3 group than Usual therapy, whereas that of prostaglandin J2 (PGJ2) and leukotriene B4, derived from arachidonic acid, was significantly decreased. As compared with Usual therapy, ω-3 PUFA therapy significantly reduced levels of triglycerides (-6.3%, P < 0.05), apolipoprotein B (-4.9%, P < 0.05) and lipoprotein(a) (-37.0%, P < 0.05) and increased nitric oxide level (62.2%, P < 0.05). In addition, the levels of these variables were positively correlated with change in 16,17-EDP and EEQs content but negatively with change in PGJ2 content.
ω-3 PUFA supplementation may improve lipid metabolism and endothelial function possibly by affecting eicosanoid metabolic status at a systemic level during convalescent healing after AMI.
URL: http://www.chictr.org.cn. Unique identifier: ChiCTR1900025859.

BACKGROUND: A Chinese herb formula Yufeining (YFN) has showed promise in the treatment of stable chronic obstructive pulmonary disease (COPD), less is known that the impact of YFN in combination with standard Western treatments on lung inflammation. This study evaluated the safety and efficacy of YFN as a treatment for stable COPD and as an anti-inflammatory agent.
METHODS: Sixty patients with stable COPD were randomly assigned to two treatment groups (YFN treatment, N = 30; placebo treatment, N = 30). Both groups received inhaled steroids and bronchodilators during an 8-week intervention, and patient status was assessed at 8 weeks later and 4 months after treatment. The primary outcome included clinical efficacy. The secondary outcomes involved CAT score, mMRC grade, six-minute walking distance (6MWD). IL-8, TNF-α, IL-17A, LTB4, TGF-β1 and CRP were also detection in peripheral serum, as well as adverse reaction conditions.
RESULTS: The YFN group demonstrated a significant improvement in clinical efficacy (compare 89.3% to 63.3% in the placebo group; P < 0.05). CAT scores and mMRC grades significantly decreased (P < 0.05, P < 0.01), and 6MWD significantly increased (P<0.05), after YFN treatment. The levels of IL-8, TNF-α, LTB4 and CRP decreased significantly after 8 weeks of treatment compared to baseline levels in both groups. Only in the YFN treatment group, the levels of IL-17A decreased significantly after treatment compared to baseline levels (P < 0.05). No changes were observed inTGF-β1 from pre-to post-treatment in either group (P > 0.05). Serum levels of IL-8, TNF-α, IL-17A, LTB4 and CRP decreased significantly after YFN treatment compared to the placebo group (P < 0.05).
CONCLUSIONS: A combinatorial treatment approach with YFN, inhaled steroids and bronchodilators produced a clinically effective treatment for stable COPD, leading to a significant decrease in circulating inflammatory mediators. The study appeared YFN was safety.
BACKGROUND: No. ChiCTR-IOR-17013577.

Inflammation causes irreparable damage in the cystic fibrosis (CF) lung. Despite high standards of care and the advent of new therapies, inflammation continues to cause significant loss of lung function and morbidity. Acebilustat is a once-daily, oral molecule with anti-inflammatory activity through the inhibition of LTA4 hydrolase and modulation of LTB4. It has potential to reduce lung function decline and pulmonary exacerbations in patients with CF and is currently being tested in a Phase II multicenter, randomized, double-blind, placebo-controlled, parallel-group study (EMPIRE-CF). Strict inclusion criteria based on modeling of the Cystic Fibrosis Foundation Patient Registry data were selected to enrich the trial with patients most likely to benefit from chronic anti-inflammatory therapy that reduces lung function decline. 200 patients between 18 and 30 years of age, with an FEV1 percent predicted (pp) ≥50%, and ≥1 exacerbation in the past year have been enrolled. Patients are randomized 1:1:1 to placebo, acebilustat 50 mg or 100 mg for 48 weeks, taken concomitantly with their current standard of care, and stratified based on concomitant CFTR modulator use, baseline FEV1pp (50% to 75% and >75%), and number of exacerbations in the past year (1 or >1). The primary endpoints are absolute change from baseline in FEV1pp and safety outcomes. Secondary endpoints include rate of pulmonary exacerbations and time to first pulmonary exacerbation. Biomarkers of inflammation will also be assessed. EMPIRE-CF is expected to identify the optimal patient population, dose, duration and endpoints for future acebilustat trials, and widen understanding of the drug\'s efficacy in patients with CF.

The high levels of eicosanoid production and the clinical efficacy of leukotriene-modifying pharmacotherapies for patients with aspirin-exacerbated respiratory disease (AERD) suggest that other interventions targeting arachidonic acid dysregulation may also improve disease control.
To assess the utility of a high omega-3/low omega-6 diet for the treatment of AERD.
Prospective, nonblinded dietary intervention in 10 adult patients with AERD at Brigham and Women\'s Hospital in Boston, MA. The primary objective was for subjects to reduce dietary omega-6 fatty acid consumption to less than 4 g/d and increase omega-3 intake to more than 3 g/d. The primary outcome was change in urinary leukotriene E4, with changes in other eicosanoids, platelet activation, lung function, and patient-reported questionnaires also assessed.
Of the 10 subjects who screened for the study, all 10 completed the dietary intervention. Urinary leukotriene E4 decreased by 0.17 ng/mg (95% CI, -0.29 to -0.04; P = .02) and tetranor prostaglandin D-M decreased by 0.66 ng/mg creatinine (95% CI, -1.21 to -0.11; P = .02). There was a 15.1-point reduction in the 22-item Sino-Nasal Outcome Test score (95% CI, -24.3 to -6.0; P = .01), a 0.27-point reduction in the 7-item Asthma Control Questionnaire score (95% CI, -0.52 to -0.03; P = .03), and no change in FEV1 % predicted (P = .92) or forced vital capacity % predicted (P = .74). All patients lost some weight over the 2-week intervention period, and there were no diet-associated adverse events.
A high omega-3/low omega-6 diet may be an appropriate adjunct treatment option for patients with AERD.