Journal of Immunotoxicology最新文献

Per- and polyfluoroalkyl substances (PFASs) are highly persistent in the environment and may cause depressed immune function. Previous studies have linked PFAS exposure to lower vaccine responses in children, but research in adults is limited. Therefore, the present study evaluated the associations between exposure to PFASs and serum antibody concentrations in adults vaccinated at age 28 years in the Faroe Islands. PFAS concentrations were determined from cord-blood collected at birth and serum samples collected at ages 7, 14, 22, and 28 years. Serum antibody concentrations against hepatitis type A and B, diphtheria, and tetanus were analyzed from blood samples collected about 6 mo after the first vaccine inoculation at age 28 years. Linear regression models were used to estimate changes in antibody concentration for each doubling of PFAS concentration. Potential effect modification by sex was assessed by including an interaction term between PFAS and sex. Although the 95% confidence intervals contain the null value, inverse trends were observed between serum perfluorooctanoate (PFOA) at ages 14 and 28 years and hepatitis type A antibody (anti-HAV) concentrations, as revealed by an estimated decrease of 0.71 (95% CI: -1.52, 0.09) and 0.24 (95% CI: -0.59, 0.10) signal-to-cutoff ratio for each doubling of exposure, respectively. Inverse trends were also observed between serum PFOA at ages 22 and 28 years and hepatitis type B antibody (anti-HBs) concentration, with an estimated decrease of 21% (95% CI: -42.20%, 7.34%) and of 17% (95% CI: -35.47%, 7.35%) in anti-HBs for each doubling of exposure, respectively. Sex-specific associations with anti-HAV were observed for cord-blood PFASs and serum PFAS concentrations at ages 7 and 14 years. No inverse associations of PFAS exposure were found with diphtheria and tetanus antibody concentrations. Future studies are needed to confirm these findings and further investigate the effects of PFASs on adult immune function.

The aging immune system is characterized by a low-grade chronic systemic inflammatory state ("inflammaging") marked by elevated serum levels of inflammatory molecules such as interleukin (IL)-6 and C-reactive protein (CRP). These inflammatory markers were also reported to be strong predictors for the development/severity of Type 2 diabetes, obesity, and COVID-19. The levels of these markers have been positively associated with those of advanced glycation end-products (AGEs) generated via non-enzymatic glycation and oxidation of proteins and lipids during normal aging and metabolism. Based on the above observations, it is clinically important to elucidate how dietary AGEs modulate inflammation and might thus increase the risk for aging-exacerbated diseases. The present narrative review discusses the potential pro-inflammatory properties of dietary AGEs with a focus on the inflammatory mediators CRP, IL-6 and ferritin, and their relations to aging in general and Type 2 diabetes in particular. In addition, underlying mechanisms - including those related to gut microbiota and the receptors for AGEs, and the roles AGEs might play in affecting physiologies of the healthy elderly, obese individuals, and diabetics are discussed in regard to any greater susceptibility to COVID-19.

Exposure to organic dust increases chronic airway inflammatory disorders. Effective treatment strategies are lacking. It has been reported that hog barn dust extracts (HDE) induce TNFα through protein kinase C (PKC) activation and that lung inflammation is enhanced in scavenger receptor A (SRA/CD204) knockout (KO) mice following HDE. Because interleukin (IL)-10 production can limit excessive inflammation, it was hypothesized here that HDE-induced IL-10 would require CD204 to effect inflammatory responses. C57BL/6 wild-type (WT), SRA KO, and IL-10 KO mice were intranasally challenged daily for 8 days with HDE and subsequently rested for 3 days with/without recombinant IL-10 (rIL-10) treatment. Primary peritoneal macrophages (PM) and murine alveolar macrophages (MH-S cells) were treated in vitro with HDE, SRA ligand (fucoidan), rIL-10, and/or PKC isoform inhibitors. HDE induced in vivo lung IL-10 in WT, but not SRA KO mice, and similar trends were demonstrated in isolated PM from same treated mice. Lung lymphocyte aggregates and neutrophils were elevated in in vivo HDE-treated SRA and IL-10 KO mice after a 3-d recovery, and treatment during recovery with rIL-10 abrogated these responses. In vitro rIL-10 treatment reduced HDE-stimulated TNFα release in MH-S and WT PM. In SRA KO macrophages, there was reduced IL-10 and PKC zeta (ζ) activity and increased TNFα following in vitro HDE stimulation. Similarly, blocking SRA (24 hr fucoidan pre-treatment) resulted in enhanced HDE-stimulated macrophage TNFα and decreased IL-10 and PKCζ activation. PKCζ inhibitors blocked HDE-stimulated IL-10, but not TNFα. Collectively, HDE stimulates IL-10 by an SRA- and PKCζ-dependent mechanism to regulate TNFα. Enhancing resolution of dust-mediated lung inflammation through targeting IL-10 and/or SRA may represent new approaches to therapeutic interventions.

The present study aimed to investigate the protective effect of quercetin on polychlorinated biphenyls (PCB)-induced liver and embryo damage in pregnant Sprague-Dawley rats. Pregnant rats were divided into five groups, and then were orally gavaged daily with peanut oil (vehicle) or a commercial PCB mixture (Aroclor 1254) - with or without co-treatment with 75, 150, or 300 mg/kg quercetin - on gestation days (GD) 4-7. At GD 9, all rats were euthanized, and their blood, liver, and uterus were collected. Expressions of CYP₄₅₀ mRNA and protein in liver, cytokines (IFNγ, IL-2, IL-4, and IL-6) and IFNγ/IL-4 ratios in liver and sera, liver morphology, and the status of implanted embryos were analyzed. The results showed Aroclor 1254 treatment alone caused hepatic cord damage (i.e. cell disorganization, swelling, decreased cytoplasm, vacuolization), and that quercetin co-treatment appeared to mitigate this damage. Similarly, levels of CYP1A1 and CYP2B1 mRNA in livers of Aroclor 1254-only-treated rats were significantly higher than those in rats co-treated with quercetin. Hepatic and sera levels of IFNγ, IL-2, IL-6, and IFNγ/IL-4 ratios, and the ratio of delayed-development embryos, all increased in Aroclor 1254-treated rats, but were relatively decreased as a result of quercetin co-treatments. IL-4 levels were decreased by Aroclor 1254 and tended to increase back to normal when quercetin was used. The results indicated that quercetin imparted a protective effect against Aroclor 1254-induced toxicity in pregnant rats, in part, by modulating levels of important pro-inflammatory cytokines and reducing induced CYP1A1 and CYP2B1 expression.