scholarly journals Increased levels of circulating LPS during Tuberculosis prevails in patients with advanced pulmonary involvement

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257214
Author(s):  
Georgina Gallucci ◽  
Natalia Santucci ◽  
Ariana Díaz ◽  
Bettina Bongiovanni ◽  
Diego Bértola ◽  
...  

Our earlier studies in tuberculosis (TB) patients indicate that in those where the process evolves to a larger pulmonary involvement, the immune endocrine response may promote an unfavorable environment. Chronic infectious diseases, and their persistent proinflammatory response, may affect mucosal barriers integrity favoring the translocation of gastrointestinal bacteria, leading to an increase of circulating lipopolysaccharides (LPS). Consequently, we quantified LPS levels in TB patients, with different degrees of pulmonary involvement, and controls (Co) and analyzed the possible relationship between LPS and inflammatory mediators i.e., C reactive protein (CRP), interleukin 6 (IL-6) and Interferon-gamma (IFN-γ), Erythrocyte Sedimentation Rate (ESR), steroid hormones (Cortisol and Dehydroepiandrosterone, DHEA), and inflammatory transcripts from peripheral blood mononuclear cells (IL-1β, IL-6, IFN-γ). LPS was assessed by the Limulus amoebocyte lysate assay and the ELISA technique was used to quantify hormones and cytokines in the plasma samples. Cytokine transcripts from PBMC were evaluated by qRT-PCR. Non-parametric tests were used. LPS levels were increased in TB patients, as did levels of CRP, IL-6, IFN-γ, cortisol and ESR. Severe patients had the highest amounts of circulating LPS; with moderate and severe cases showing much higher levels of CRP, ESR, IL-6, IFN-γ and cortisol/DHEA ratio, as an endocrine imbalance. Only in PBMC from severe cases was mRNA for IL-1β increased. Correlation analysis showed that levels of LPS from severe patients were positively associated with IL-6 and IFN-γ plasma concentrations and with IL-1β transcripts, while IL-6 had a positive correlation with the cortisol/DHEA ratio. The higher levels of circulating LPS during progressive TB may emerge as a contributing factor for the persistence of the greater immune endocrine imbalance distinctive of advanced disease, which might suggest a vicious cycle among LPS, inflammation and endocrine imbalance.

2019 ◽  
Vol 3 (6) ◽  
pp. 1003-1013 ◽  
Author(s):  
Krystallenia I Alexandraki ◽  
Nikolaos V Apostolopoulos ◽  
Christos Adamopoulos ◽  
Evangelia Stamouli ◽  
Georgia Dalagiorgou ◽  
...  

Abstract Background Neuroinflammation, impaired brain insulin signaling, and neuronal apoptosis may be interrelated in the pathophysiology of people with Alzheimer disease (AD) and diabetes, either type 1 or 2 diabetes (T1D or T2D, respectively). Methods We studied 116 patients: 41 with AD, 20 with T1D, 21 with T2D, and 34 healthy controls. The number (n) of cytokine-secreting peripheral blood mononuclear cells (PBMCs) before and after mitogenic stimulation was determined for interleukin 1β (IL1β), interleukin 6 (IL6), tumor necrosis factor (TNF) by the enzyme-linked-immuno-spot assay. Serum concentrations of C-reactive protein (CRP) and Fas ligand (FASLG) were determined by ELISA. Results The studied subgroups did not differ in sex but differed in age. Higher CRP concentrations were detected in the AD group than in the T1D group (P = 0.02) and lower in controls (P < 0.001). The nPBMCs was higher in AD patients after stimulation than in basal conditions: after stimulation in nTNF (P < 0.001 vs T2D; P < 0.001 vs T1D; P = 0.001 vs control), nIL6 (P = 0.039 vs T2D; P < 0.001 vs T1D; P = 0.007 vs control), and nIL1β (P = 0.03 vs control). The nPBMCs increased after stimulation with ΡΜA in all the subgroups (P < 0.001). FASLG in the AD group displayed statistically higher concentrations than in all other subgroups (P < 0.001 vs T2D; P < 0.001 vs T1D; P = 0.012 vs control). The nPBMCs was positively correlated with plasma concentrations of FASLG in the AD subgroup. Conclusions Patients with AD display a low-grade systemic inflammation compared to people with diabetes. The FAS–FASLG pathway has a potential role because FASLG concentrations are positively correlated with the inflammatory response in AD. However, this positive correlation cannot be seen in people with diabetes, at least not with the apoptotic markers used in the present study.


2018 ◽  
Vol 17 (6) ◽  
pp. 430-438 ◽  
Author(s):  
Mina Abdolahi ◽  
Payam Sarraf ◽  
Mohammad Hassan Javanbakht ◽  
Niyaz Mohammadzadeh Honarvar ◽  
Mahsa Hatami ◽  
...  

Background: Migraine is a disabling neuroinflammatory condition characterized by increasing the levels of interleukin (IL)-6, a proinflammatory cytokine and C-reactive protein (CRP) which considered as a vascular inflammatory mediator, disrupting the integrity of blood-brain barrier and contributing to neurogenic inflammation, and disease progression. Curcumin and ω-3 fatty acids can exert neuroprotective effects through modulation of IL-6 gene expression and CRP levels. The aim of present study is the evaluation of combined effects of ω-3 fatty acids and nano-curcumin supplementation on IL-6 gene expression and serum level and hs-CRP levels in migraine patients. Methods: Eighty episodic migraine patients enrolled in the trial and were divided into four groups as 1) combination of ω-3 fatty acids (2500 mg) plus nano-curcumin (80 mg), 2) ω-3 (2500 mg), 3) nanocurcumin (80 mg), and 4) the control (ω-3 and nano-curcumin placebo included oral paraffin oil) over a two-month period. At the beginning and the end of the study, the expression of IL-6 from peripheral blood mononuclear cells and IL-6 and hs-CRP serum levels were measured, using a real-time PCR and ELISA methods, respectively. Results: The results showed that both of ω-3 and nano-curcumin down-regulated IL-6 mRAN and significantly decreased the serum concentration. hs-CRP serum levels significantly decrease in combination and nano-curcumin within groups (P<0.05). An additive greater reduction of IL-6 and hs-CRP was observed in the combination group suggested a possible synergetic relation. Conclusion: It seems that ω-3 fatty acids and curcumin supplementation can be considered a new promising target in migraine prevention.


2020 ◽  
Vol 10 (2) ◽  
pp. 271-275
Author(s):  
Ying Li ◽  
Yongshan Tang

Sepsis is a common clinical disease. The NLRP3 inflammasome is a multiprotein complex that is involved in both innate and adaptive immune responses. However, the expression of NLRP3 in patients with sepsis has not been elucidated. 98 patients with sepsis before and after treatment were selected and 106 healthy volunteers were used as the control group. PBMCs were isolated from each group to measure NLRP3 and Caspase 1 level Real time PCR. The expression of serum procalcitonin (PCT), C-reactive protein (CRP), IL-1β and IL-18 was analyzed by ELISA. NLRP3 and Caspase 1 level was significantly increased in sepsis patients before treatment with increased secretion of IL-1β and IL-18 in serum and elevated level of PCT and CRP (P < 0.05). NLRP3, Caspase 1 expression, IL-1β and IL-18 secretion were positively correlated with serum PCT and CRP in patients with sepsis (P < 0.05). After treatment, NLRP3 and Caspase 1 mRNA expression was significantly decreased and serum IL-1β and IL-18 secretion was significantly decreased (P < 0.05). NLRP3 is increased in sepsis and IL-1β and IL-18 secretion is elevated, implying the involvement of NLRP3 in the occurrence and development of sepsis.


Blood ◽  
2003 ◽  
Vol 102 (8) ◽  
pp. 2786-2788 ◽  
Author(s):  
Anne-Geneviève Marcelin ◽  
Laurent Aaron ◽  
Christine Mateus ◽  
Emmanuel Gyan ◽  
Isabelle Gorin ◽  
...  

Abstract To assess the clinical benefit of rituximab for HIV-associated Castleman disease, 5 patients infected with HIV with histologic-proven Castleman disease were prospectively enrolled to receive 4 infusions of rituximab. Clinical and biologic parameters (C-reactive protein, CD19 cell count, Kaposi sarcoma–associated herpesvirus [KSHV] viral load in peripheral blood mononuclear cells) were assessed before and at different time points following rituximab infusions. Two patients died very quickly after the beginning of rituximab therapy with no effect on both KSHV viral load and CD19 cell count. Three of 5 patients were considered in complete remission with no more clinical symptoms related to Castleman disease with a follow-up of 4 to 14 months. In 2 cases, clinical remission correlated with a dramatic decrease of KSHV viral load and C-reactive protein levels and a transitory but sharp decrease of CD19 cell count. In 2 responders, we observed an aggravation of Kaposi sarcoma. Our preliminary results suggest that rituximab may be effective in controlling Castleman disease in a subset of patients, although it may exacerbate concomitant Kaposi sarcoma.


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