scholarly journals Serum Levels of Pro-inflammatory Cytokines in relationship to outcomes in Children with P. falciparum malaria, in Nnewi-South east Nigeria

1970 ◽  
Vol 42 (2) ◽  
pp. 142-146
Author(s):  
EC Okocha ◽  
NC Ibeh ◽  
EO Ukaejiofor ◽  
JC Ebenebe ◽  
JC Aneke ◽  
...  

Background and Objective: In P. falciparum malaria (PFM) infestation there are marked changes in cytokine production as the body mounts an immune response to it. Hence we set out to study these changes.Methods: A total of 158 cases of PFM among children attending the paediatric unit of our hospital and 56 healthy controls were studied. Children with febrile illness were screened for malaria using 10% Giemsa stained blood smear. Patients with positive smears were recruited; co-infected patients – those infected by another organism in addition to plasmodium specie.- were excluded. Whole blood was collected, some into plain tubes for serum cytokine testing and some into EDTA bottles for complete blood count and parasite density (PD) determination. Controls with asymptomatic parasitaemia were excluded.Results: Using the World Health Organization criteria for defining severe malaria; we identified 15 cases of severe and 143 cases of uncomplicated PFM. Significantly elevated levels of interleukin-1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were seen in the uncomplicated and severe forms of PFM. It was observed that the elevated cytokine values correlated with PD (in uncomplicated PFM but not in the severe forms). The difference between PD/absolute monocyte count (AMC) ratio was not significant (p=0.13); while PD/platelet count (PC) and PC/ AMC ratios were significant (p=0.01, and 0.03 respectively) when compared between uncomplicated and severe disease.Conclusion: Our data seems to suggest that subjects with an adequate immune response to the parasite density, in terms of pro-inflammatory cytokine levels, presented with uncomplicated disease; while those who have an inadequate response presented with severe disease. The ratios of (PD/PC) and (PC/AMC), in the positive and negative directions respectively, may be predictors of increased disease severity. These observations may have implications for predicting disease outcome and PFM therapy.Key Words: plasmodium falciparum malaria, pro-inflammatory cytokines, Parasite density/Platelet count ratio, Platelet count/Absolute monocyte

2020 ◽  
Author(s):  
DANIEL OSAGIE OKPOKOR ◽  
ASAGA MAC PETER ◽  
Ajibaye Olusola ◽  
Anthony Danaan Dakul

Abstract Background Available evidence indicates that the various stages of the malaria parasite life cycle have specific immune responses. The pro-inflammatory cytokines tend to play an important role in preventing malaria and killing the parasites. Furthermore, the relative levels of pro-and anti-inflammatory cytokines are essential mediators of malaria anemia production and outcomes. Natural human immune responses to malaria recognize extracellular sporozoites and merozoites, both of which have surface-exposed antigens, and which are currently being developed for various vaccines. Methods A total of four hundred sixty- two (462) participants were tested for Plasmodium falciparum. The procedure employed were parasite staining using World Health Organization parasitology laboratory protocol [Microscopy] of Giemsa staining and Enzyme linked immunosorbent assay [ELISA]. Results The subjects in this study showed high levels of INF-γ and TNF-α which decreases with increased malaria severity and high parasite density. These results suggest that INF-γ cytokine and TNF-α may contribute to protection against severe malaria anaemia and parasite clearance. Conversely, infected participants showed higher levels of IL-10, which decreases with severe malaria parasite, furthermore IL-10 levels correlated with parasite density. These findings suggest that higher levels of anti-inflammatory cytokines, especially IL-10 levels may contribute to pathogenesis of complicated malaria by inhibiting the INF-γ and TNF-α production. Conclusion Molecular biological and other serological analysis are needed to elucidate the implication of these cytokines and other pro-inflammatory cytokines as IL-17, IL-21 and IL-22 in the responses to malaria and consequently their involvement in malaria vaccine construct/development as well as other therapeutics for the treatment and elimination of the malaria parasite in our environment.


2020 ◽  
Author(s):  
Daniel Osegi Okpokor ◽  
Olusola Ajibaye ◽  
Peter Mac Asaga ◽  
Ikechukwu Nwankwo ◽  
Anthony Danaan Dakul

Abstract Background Available evidence indicates that the various stages of the malaria parasite life cycle elicit specific immune responses of which the relative levels of pro-inflammatory cytokines are key to disease progression, killing the parasite and mediating disease outcomes. This study will inform immunological interventions against malaria and thus malaria vaccine developments programs/efforts. Methods A total of four hundred and sixty-two participants were screened in a community survey for Plasmodium falciparum (P. falciparum) malaria in Baiyeku, Lagos, Nigeria. P. falciparum parasitaemia was determined by Microscopy using thick and thin blood films stained by Giemsa method using World Health Organization parasitology laboratory protocol whist the serum levels of IL-10, IFNγ and TNFα were determined by Enzyme linked immunosorbent assay [ELISA]. Data analysis was done by One-way Analysis of Variance (ANOVA), Chi square (X²) and Student’s T-test in statistical package for the social sciences (SPSS) version 24 was used to test statistical significance between the symptomatic groups and asymptomatic in relation to age, gender and BMI of the participants.Results A total of 70 (15.2 %) participants were microscopically positive for P. falciparum of which 70% were female, 30% were males while children aged 1-17 years were 65.7%. The geometric mean parasite density (GMPD) was significantly (p=0.001) higher among females than males. The GMPD of participants < 5 years was also significantly (p=0.001) higher than other age groups. About 46.8% of the participants were underweight (BMI < 18.5) also had the highest parasite intensity. The TNFα, IFNγ and IL-10 levels were significantly (p 0.05) higher in the infected than the uninfected participants. IFN-γ values were significantly (p=0.014) elevated among the symptomatic than the asymptomatic participants while there was no significant difference (P>0.053) in the levels of TNF-α and IL-10 (P>0.093) between the symptomatic and asymptomatic participants. Notably, the IL-10 levels were the most elevated amongst the participants with the highest parasite density.Conclusion The prevalence of P. falciparum obtained in this study area which is endemic for malaria is 15.2% suggesting a significant reduction of the disease over time. The awareness of the disease which is now more than before seems to contribute to the lowering of prevalence of the disease in the community. There was a positive relationship between TNF-alpha levels and body temperature. However, compared with the anti-inflammatory cytokine (IL-10) in this study, the levels of the pro-inflammatory cytokines (IFN-γ and TNF-α) were lower due to the negative action of the anti-inflammatory cytokines. IL-10 value increased as parasitemia increased (p=0.073). These findings suggest that higher levels of anti-inflammatory cytokines, especially IL-10 levels may contribute to pathogenesis of uncomplicated malaria.


Author(s):  
Bruna Lima Correa ◽  
Nadia El Harane ◽  
Ingrid Gomez ◽  
Hocine Rachid Hocine ◽  
José Vilar ◽  
...  

Abstract Aims The cardioprotective effects of human induced pluripotent stem cell-derived cardiovascular progenitor cells (CPC) are largely mediated by the paracrine release of extracellular vesicles (EV). We aimed to assess the immunological behaviour of EV-CPC, which is a prerequisite for their clinical translation. Methods and results Flow cytometry demonstrated that EV-CPC expressed very low levels of immune relevant molecules including HLA Class I, CD80, CD274 (PD-L1), and CD275 (ICOS-L); and moderate levels of ligands of the natural killer (NK) cell activating receptor, NKG2D. In mixed lymphocyte reactions, EV-CPC neither induced nor modulated adaptive allogeneic T cell immune responses. They also failed to induce NK cell degranulation, even at high concentrations. These in vitro effects were confirmed in vivo as repeated injections of EV-CPC did not stimulate production of immunoglobulins or affect the interferon (IFN)-γ responses from primed splenocytes. In a mouse model of chronic heart failure, intra-myocardial injections of EV-CPC, 3 weeks after myocardial infarction, decreased both the number of cardiac pro-inflammatory Ly6Chigh monocytes and circulating levels of pro-inflammatory cytokines (IL-1α, TNF-α, and IFN-γ). In a model of acute infarction, direct cardiac injection of EV-CPC 2 days after infarction reduced pro-inflammatory macrophages, Ly6Chigh monocytes, and neutrophils in heart tissue as compared to controls. EV-CPC also reduced levels of pro-inflammatory cytokines IL-1α, IL-2, and IL-6, and increased levels of the anti-inflammatory cytokine IL-10. These effects on human macrophages and monocytes were reproduced in vitro; EV-CPC reduced the number of pro-inflammatory monocytes and M1 macrophages, while increasing the number of anti-inflammatory M2 macrophages. Conclusions EV-CPC do not trigger an immune response either in in vitro human allogeneic models or in immunocompetent animal models. The capacity for orienting the response of monocyte/macrophages towards resolution of inflammation strengthens the clinical attractiveness of EV-CPC as an acellular therapy for cardiac repair.


2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Lianci Peng ◽  
Maaike R. Scheenstra ◽  
Roel M. van Harten ◽  
Henk P. Haagsman ◽  
Edwin J. A. Veldhuizen

Abstract Cathelicidins (CATHs) play an important role in the innate immune response against microbial infections. Among the four chicken cathelicidins, CATH-B1 is studied the least. In this study, the effect of CATH-B1 on the macrophage response towards avian pathogenic E. coli (APEC) and bacterial ligands was investigated. Our results show that APEC induced CATH-B1 gene expression in both a chicken macrophage cell line (HD11 cells) and primary macrophages, while expression of the other three CATHs was virtually unaffected. While the antimicrobial activity of CATH-B1 is very low under cell culture conditions, it enhanced bacterial phagocytosis by macrophages. Interestingly, CATH-B1 downregulated APEC-induced gene expression of pro-inflammatory cytokines (IFN-β, IL-1β, IL-6 and IL-8) in primary macrophages. In addition, CATH-B1 pre-incubated macrophages showed a significantly higher gene expression of IL-10 after APEC challenge, indicating an overall anti-inflammatory profile for CATH-B1. Using isothermal titration calorimetry (ITC), CATH-B1 was shown to bind LPS. This suggests that CATH-B1 reduces toll like receptor (TLR) 4 dependent activation by APEC which may partly explain the decreased production of pro-inflammatory cytokines by macrophages. On the contrary, direct binding of CATH-B1 to ODN-2006 enhanced the TLR21 dependent activation of macrophages as measured by nitric oxide production. In conclusion, our results show for the first time that CATH-B1 has several immunomodulatory activities and thereby could be an important factor in the chicken immune response.


2020 ◽  
Vol 48 (08) ◽  
pp. 1875-1893
Author(s):  
Da-Sol Kim ◽  
Kyoung-Eun Park ◽  
Yeon-Ju Kwak ◽  
Moon-Kyoung Bae ◽  
Soo-Kyung Bae ◽  
...  

Inflammation regulation is essential for maintaining healthy functions and normal homeostasis of the body. Porphyromonas gingivalis (P. gingivalis) is a gram-negative anaerobic bacterium and a major pathogen that causes oral inflammation and other systemic inflammations. This study aims to examine the anti-inflammatory effects of Agrimonia pilosa Ledeb root extracts (APL-ME) in Porphyromonas gingivalis LPS-induced RAW 264.7 cells and find anti-inflammatory effect compounds of APL-ME. The anti-inflammatory effects of APL-ME were evaluated anti-oxidant activity, cell viability, nitrite concentration, pro-inflammatory cytokines (interleukin-1[Formula: see text], interleukin-6, tumor necrosis factor (TNF)-[Formula: see text], and anti-inflammatory cytokine (interleukin-10 (IL-10)). Also, Inflammation related genes and proteins, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), expression were decreased by APL-ME and mitogen-activated protein kinase (MAPK) signaling proteins expression was regulated by APL-ME. Liquid chromatography-mass spectrometer (LC/MS)-MS analysis results indicated that several components were detected in APL-ME. Our study indicated that APL-ME suppressed nitrite concentrations, pro-inflammatory cytokines such as IL-1[Formula: see text], IL-6 and TNF-[Formula: see text] in P. gingivalis LPS induced RAW 264.7 cells. However, IL-10 expression was increased by ALP-ME. In addition, protein expressions of COX-2 and iNOS were inhibited APL-ME extracts dose-dependently. According to these results, APL-ME has anti-inflammatory effects in P. gingivalis LPS induced RAW 264.7 cells.


2017 ◽  
Vol 1 (16) ◽  
pp. 1274-1286 ◽  
Author(s):  
Marcela Gatica-Andrades ◽  
Dimitrios Vagenas ◽  
Jessica Kling ◽  
Tam T. K. Nguyen ◽  
Helen Benham ◽  
...  

Key Points Differential expression of WNT ligands in patients with septic shock and a mouse model of endotoxemia correlates with inflammatory cytokines. WNT ligands and WNT/β-catenin signaling positively regulate lipopolysaccharide-induced pro-inflammatory cytokines without impairing IL-10.


2021 ◽  
Author(s):  
Brenda Ramírez-Aguero ◽  
Javier Serrato-Salas ◽  
José Luis Montiel-Hernández ◽  
Judith González-Christen

AbstractSeveral pathogenic mechanisms have been linked to the severity of dengue virus infection, like viral cytotoxicity, underlying host genetics and comorbidities such as diabetes and dyslipidemia. It has been observed that patients with severe manifestations develop an uncontrolled immune response, with an increase in pro-inflammatory cytokines such as TNF, IL-1β, IL-8, IL-6 and chemokines that damage the human microvascular endothelium, and also in anti-inflammatory cytokines IL-4, IL-10 and TGF-β1. The role of TGF-β1 on dengue is not clear; few studies have been published, and most of them from patient sera data, with both protective and pathological roles have described. The aim of this study was to evaluate the ability of TGF-β1 to regulate the secretion of IL-1β in macrophages infected by DENV using THP-1 cells treated with recombinant TGF-β1 before or after DENV infection. By RT-PCR we did not observe a difference in IL-1β expression between infected cells pretreated with TGF-β1 and those that were not. However, secretion of IL-1β was reduced only in cells stimulated with TGF-β1 before infection, and not in those treated 2 hours post-infection. TGF-β1 receptor blockage with SB505124 inhibitor, prior to the addition of TGF-β1 and infection, abrogated the inhibitory effect of TGF-β1. Our results suggest that DENV could regulate the function of TGF-β1 on macrophages. This negative regulation of the TGF-β1 pathway could be used by DENV to evade the immune response and could contribute to the immunopathology.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9031-9031
Author(s):  
Chelsea D. Gilts ◽  
Patricia A. Parker ◽  
Curtis A. Pettaway ◽  
Lorenzo Cohen

9031 Background: It is important to identify factors that predict who will benefit the most from psychosocial interventions in cancer populations. Methods: We examined the association between pretreatment psychosocial factors and subjective and objective outcomes from a brief cognitive-behavioral stress management program. This three-arm randomized clinical trial investigated the effects of a presurgical stress management (SM; n=53) compared to supportive attention (SA; n=54) and standard care (SC; n=52) on quality of life (QOL) and immune outcomes in men with prostate cancer scheduled for radical prostatectomy. We previously reported improved QOL 1 year after surgery in the SM and SA groups compared to the SC group and higher pro-inflammatory cytokines 48h after surgery in the SM group. We investigated the moderating effects of baseline psychosocial factors (social support (SS), dyadic adjustment (DA), distress (BSIGSI), and impact of event (IES)), on QOL (SF-36 physical (PCS) and mental (MCS) component scores) 1 year after surgery and immune response 48h after surgery. Results: Baseline SS and BSIGSI interacted with group in predicting PCS 1 year after surgery (p’s <.05). Men who reported low baseline SS and were in SM had increased PCS 1 year after surgery compared to men with low SS in the SC group (b=.36, p<.01). Conversely, men who reported high BSIGSI at baseline and were in SA had increased PCS 1 year after surgery compared to those in SM (b=11.14, p=.03), with SC having an intermediate nonsignificant effect. All four psychosocial factors (SS, DA, BSIGSI, IES) interacted with group in predicting changes in pro-inflammatory cytokines (interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor, and interferon) 48h post-surgery (all p’s <.04). In all significant interactions, men who reported greater psychosocial vulnerability at baseline and were in SM had increased immune response 48h after surgery compared to psychosocially vulnerable men in either SC (all p’s <.02) or SA (all p’s <.02). Conclusions: These findings suggest that baseline psychosocial factors are important indicators of who may benefit most from a SM intervention on both subjective and objective outcomes.


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