scholarly journals Fat meets the cholinergic antiinflammatory pathway

2005 ◽  
Vol 202 (8) ◽  
pp. 1017-1021 ◽  
Author(s):  
Kevin J. Tracey

The cholinergic antiinflammatory pathway is a neural mechanism that is controlled by the vagus nerve and inhibits local cytokine release, thereby preventing the damaging effects of cytokine overproduction. A new study now shows that dietary fat can activate this pathway, a finding that may help explain the immune system's failure to react to food antigens and commensal bacteria. Here we discuss this new data and its potential implications for dietary intervention in the treatment of inflammatory diseases.

2017 ◽  
Vol 114 (38) ◽  
pp. 10178-10183 ◽  
Author(s):  
Hana Sarashina-Kida ◽  
Hideo Negishi ◽  
Junko Nishio ◽  
Wataru Suda ◽  
Yuki Nakajima ◽  
...  

The commensal microbiota within the gastrointestinal tract is essential in maintaining homeostasis. Indeed, dysregulation in the repertoire of microbiota can result in the development of intestinal immune–inflammatory diseases. Further, this immune regulation by gut microbiota is important systemically, impacting health and disease of organ systems beyond the local environment of the gut. What has not been explored is how distant organs might in turn shape the microbiota via microbe-targeted molecules. Here, we provide evidence that surfactant protein D (SP-D) synthesized in the gallbladder and delivered into intestinal lumen binds selectively to species of gut commensal bacteria. SP-D–deficient mice manifest intestinal dysbiosis and show a susceptibility to dextran sulfate sodium-induced colitis. Further, fecal transfer from SP-D–deficient mice to wild-type, germ-free mice conveyed colitis susceptibility. Interestingly, colitis caused a notable increase inSftpdgene expression in the gallbladder, but not in the lung, via the activity of glucocorticoids produced in the liver. These findings describe a unique mechanism of interorgan regulation of intestinal immune homeostasis by SP-D with potential clinical implications such as cholecystectomy.


2021 ◽  
Vol 4 (1) ◽  
pp. 17-20
Author(s):  
Nazanin Ashtar Nakhaei ◽  
◽  
Amir Hossein Norooznezhad ◽  

Coronavirus Disease 2019 (COVID-19) is one of the most critical health issues in the world. According to the findings, systemic proinflammatory cytokine release is associated with the pathogenesis of cytokine storm, contributing to morbidities and even mortality in patients diagnosed with COVID-19. Among pregnant patients diagnosed with COVID-19, preterm labor is one of the most crucial side effects, with a prevalence of up to 63.8% in some studies. As well as cytokine storm, proinflammatory cytokines are involved in preterm labor. Mesenchymal Stem Cells (MSCs) transplantation has been used in different trials to suppress inflammation in many inflammatory diseases. MSCs have also been successfully applied to treat patients diagnosed with COVID-19, considering the cytokine storm in these patients. So, it is possible to use the transplantation of MSCs derived from the maternal side of the placenta as an autologous product to suppress cytokine storm in critically ill patients diagnosed with COVID-19. The autologous transplantation of MSCs helps to suppress cytokine storm and systemic inflammation. Inhibition of systemic cytokine release could prevent poor outcomes, especially mortality and morbidities in the mentioned patients.


2020 ◽  
Vol 38 (13) ◽  
pp. 1419-1428 ◽  
Author(s):  
Rowan T. Chlebowski ◽  
Aaron K. Aragaki ◽  
Garnet L. Anderson ◽  
Kathy Pan ◽  
Marian L. Neuhouser ◽  
...  

PURPOSE Observational studies of dietary fat intake and breast cancer have reported inconsistent findings. This topic was addressed in additional analyses of the Women’s Health Initiative (WHI) Dietary Modification (DM) clinical trial that evaluated a low-fat dietary pattern influence on breast cancer incidence. METHODS In the WHI DM trial, 48,835 postmenopausal women, ages 50-79 years, with no prior breast cancer, and a dietary fat intake of ≥ 32% of energy were randomly assigned at 40 US centers to a usual diet comparison group (60%) or dietary intervention group (40%). The goals were to reduce fat intake to 20% of energy and increase vegetable, fruit, and grain intake. Breast cancers were confirmed after central medical record review and serial National Death Index linkages to enhance mortality findings. RESULTS During 8.5 years of dietary intervention, breast cancer incidence and deaths as a result of breast cancer were nonsignificantly lower in the intervention group, while deaths after breast cancer were statistically significantly lower both during intervention and through a 16.1-year (median) follow-up. Now, after a long-term, cumulative 19.6-year (median) follow-up, the significant reduction in deaths after breast cancer persists (359 [0.12%] v 652 [0.14%] deaths; hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.96; P = .01), and a statistically significant reduction in deaths as a result of breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (132 [0.037%, annualized risk] v 251 [0.047%] deaths, respectively; HR, 0.79; 95% CI, 0.64 to 0.97; P = .02). CONCLUSION Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, may reduce the risk of death as a result of breast cancer in postmenopausal women.


2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Isabelle Naegelen ◽  
Nicolas Beaume ◽  
Sébastien Plançon ◽  
Véronique Schenten ◽  
Eric J. Tschirhart ◽  
...  

Neutrophils participate in the maintenance of host integrity by releasing various cytotoxic proteins during degranulation. Due to recent advances, a major role has been attributed to neutrophil-derived cytokine secretion in the initiation, exacerbation, and resolution of inflammatory responses. Because the release of neutrophil-derived products orchestrates the action of other immune cells at the infection site and, thus, can contribute to the development of chronic inflammatory diseases, we aimed to investigate in more detail the spatiotemporal regulation of neutrophil-mediated release mechanisms of proinflammatory mediators. Purified human neutrophils were stimulated for different time points with lipopolysaccharide. Cells and supernatants were analyzed by flow cytometry techniques and used to establish secretion profiles of granules and cytokines. To analyze the link between cytokine release and degranulation time series, we propose an original strategy based on linear fitting, which may be used as a guideline, to (i) define the relationship of granule proteins and cytokines secreted to the inflammatory site and (ii) investigate the spatial regulation of neutrophil cytokine release. The model approach presented here aims to predict the correlation between neutrophil-derived cytokine secretion and degranulation and may easily be extrapolated to investigate the relationship between other types of time series of functional processes.


2013 ◽  
Vol 110 (5) ◽  
pp. 871-879 ◽  
Author(s):  
Bengt Vessby ◽  
Inga-Britt Gustafsson ◽  
Siv Tengblad ◽  
Lars Berglund

Δ9-Desaturase (stearoyl-CoA desaturase 1, SCD-1) regulates the desaturation of SFA, mainly stearic and palmitic, to MUFA. Δ6-Desaturase (D6D) and Δ5-desaturase (D5D) are involved in the metabolism of linoleic and α-linolenic acid to polyunsaturated metabolites. The objective of the present study was to study the effects of different types of dietary fat on indices of fatty acid desaturase (FADS) activity (evaluated as product:precursor ratios) in plasma and skeletal muscle in human subjects. A high SCD-1 index has been related to obesity and metabolic disorders, while the D5D index is associated with insulin sensitivity. Fatty acid composition of serum and skeletal muscle lipids was analysed by GLC during a randomised, controlled, 3-month dietary intervention in healthy subjects. A comparison of the effects of a diet containing butter fat (SFA, n 17) with a diet containing monounsaturated fat (MUFA, n 17), keeping all other dietary components constant, showed a reduced SCD-1 activity index by 20 % on the MUFA diet compared with the SFA diet assessed in serum cholesteryl esters. The D6D and D5D indices remained unaffected. Supplementation with long-chain n-3 fatty acids reduced the SCD-1 index by a similar magnitude while the D6D index decreased and the D5D index increased. It is concluded that changes in the type of fat in the diet affect the indices of FADS activity in serum and skeletal muscle in human subjects. The desaturase activity indices estimated from the serum lipid ester composition are significantly related to corresponding indices studied in skeletal muscle phospholipids.


2010 ◽  
Vol 104 (9) ◽  
pp. 1357-1362 ◽  
Author(s):  
Helena Petersson ◽  
Ulf Risérus ◽  
Jolene McMonagle ◽  
Hanne L. Gulseth ◽  
Audrey C. Tierney ◽  
...  

Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P = 0·83; 15-keto-dihydro-PGF2α, P = 0·45; and CRP, P = 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.


2008 ◽  
Vol 101 (5) ◽  
pp. 750-759 ◽  
Author(s):  
Danielle I. Shaw ◽  
Audrey C. Tierney ◽  
Sinead McCarthy ◽  
Jane Upritchard ◽  
Susan Vermunt ◽  
...  

Controlled human intervention trials are required to confirm the hypothesis that dietary fat quality may influence insulin action. The aim was to develop a food-exchange model, suitable for use in free-living volunteers, to investigate the effects of four experimental diets distinct in fat quantity and quality: high SFA (HSFA); high MUFA (HMUFA) and two low-fat (LF) diets, one supplemented with 1·24 g EPA and DHA/d (LFn-3). A theoretical food-exchange model was developed. The average quantity of exchangeable fat was calculated as the sum of fat provided by added fats (spreads and oils), milk, cheese, biscuits, cakes, buns and pastries using data from the National Diet and Nutrition Survey of UK adults. Most of the exchangeable fat was replaced by specifically designed study foods. Also critical to the model was the use of carbohydrate exchanges to ensure the diets were isoenergetic. Volunteers from eight centres across Europe completed the dietary intervention. Results indicated that compositional targets were largely achieved with significant differences in fat quantity between the high-fat diets (39·9 (sem0·6) and 38·9 (sem0·51) percentage energy (%E) from fat for the HSFA and HMUFA diets respectively) and the low-fat diets (29·6 (sem0·6) and 29·1 (sem0·5) %E from fat for the LF and LFn-3 diets respectively) and fat quality (17·5 (sem0·3) and 10·4 (sem0·2) %E from SFA and 12·7 (sem0·3) and 18·7 (sem0·4) %E MUFA for the HSFA and HMUFA diets respectively). In conclusion, a robust, flexible food-exchange model was developed and implemented successfully in the LIPGENE dietary intervention trial.


2021 ◽  
Vol 12 ◽  
Author(s):  
Chengxin Luan ◽  
Junjie Zhou ◽  
Haixia Wang ◽  
Xiaoyu Ma ◽  
Zhangbiao Long ◽  
...  

Chimeric antigen receptor T (CAR-T) cell therapy has achieved remarkable clinical efficacy in treatment of many malignancies especially for B-cell hematologic malignancies. However, the application of CAR-T cells is hampered by potentially adverse events, of which cytokine release syndrome (CRS) is one of the severest and the most studied. Local cytokine-release syndrome (L-CRS) at particular parts of the body has been reported once in a while in B-cell lymphoma or other compartmental tumors. The underlying mechanism of L-CRS is not well understood and the existing reports attempting to illustrate it only involve compartmental tumors, some of which even indicated L-CRS only happens in compartmental tumors. Acute lymphoblastic leukemia (ALL) is systemic and our center treated a B-cell ALL patient who exhibited life threatening dyspnea, L-CRS was under suspicion and the patient was successfully rescued with treatment algorithm of CRS. The case is the firstly reported L-CRS related to systemic malignancies and we tentatively propose a model to illustrate the occurrence and development of L-CRS of systemic malignancies inspired by the case and literature, with emphasis on the new recognition of L-CRS.


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