scholarly journals Interacting Roles of Immune Mechanisms and Viral Load in the Pathogenesis of Crimean-Congo Hemorrhagic Fever

2010 ◽  
Vol 17 (7) ◽  
pp. 1086-1093 ◽  
Author(s):  
Ana Saksida ◽  
Darja Duh ◽  
Branka Wraber ◽  
Isuf Dedushaj ◽  
Salih Ahmeti ◽  
...  
Keyword(s):  
Viral Load ◽  
Antibody Response ◽  
Fatal Outcome ◽  
Hemorrhagic Fever ◽  
Interleukin 10 ◽  
The Body ◽  
Necrosis Factor Alpha ◽  
Crimean Congo Hemorrhagic Fever ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Until now, the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) has not been well described. However, it has been hypothesized that it could be a result of the direct injury of virus-infected tissues in combination with the indirect effects of host immune responses, including cytokines. To shed more light on the role of viral load and cytokines, differential influences of CCHF virus (CCHFV) RNA load, antibody response, and cytokine production on severity and outcome of the disease were studied in sera of 46 patients with confirmed acute CCHF from Kosovo. In this study, viral load proved to be strongly related to the severity and outcome of the disease, with higher viral loads detected in patients with fatal outcomes than in surviving patients. Also, patients with fatal outcome had on average a weaker antibody response, if one was present at all. High levels of interleukin-10 (IL-10), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) were associated with poor outcome, since detected concentrations were highest in patients with fatal outcome and lowest in patients with moderate disease course. Additionally, a positive linear dependence between viral load and these cytokines was observed. Interestingly, reduced levels of IL-12 were detected in all CCHF patients. Our study favors the hypothesis that CCHF could be a result of a delayed and downregulated immune response caused by IL-10, which leads to an increased replication and spread of CCHFV throughout the body. This consequently triggers increased production of IFN-γ and TNF-α, cytokines mediating vascular dysfunction, disseminated intravascular coagulation, organ failure, and shock.

scholarly journals Characterization of Biomarker Levels in Crimean–Congo Hemorrhagic Fever and Hantavirus Fever with Renal Syndrome

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 686 ◽  
Author(s):  
Miša Korva ◽  
Katarina Resman Rus ◽  
Miša Pavletič ◽  
Ana Saksida ◽  
Nataša Knap ◽  
...  
Keyword(s):  
Viral Load ◽  
Severe Disease ◽  
Fatal Outcome ◽  
Febrile Illness ◽  
Hemorrhagic Fever ◽  
Control Group ◽  
Serum Samples ◽  
Crimean Congo Hemorrhagic Fever ◽  
Tnf Α

Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are important viral hemorrhagic fevers (VHF), especially in the Balkan region. Infections with Dobrava or Puumala orthohantavirus and Crimean-Congo hemorrhagic fever orthonairovirus can vary from a mild, nonspecific febrile illness, to a severe disease with a fatal outcome. The pathogenesis of both diseases is poorly understood, but it has been suggested that a host’s immune mechanism might influence the pathogenesis of the diseases and survival. The aim of our study is to characterize cytokine response in patients with VHF in association with the disease progression and viral load. Forty soluble mediators of the immune response, coagulation, and endothelial dysfunction were measured in acute serum samples in 100 HFRS patients and 70 CCHF patients. HFRS and CCHF patients had significantly increased levels of IL-6, IL-12p70, IP-10, INF-γ, TNF-α, GM-CSF, MCP-3, and MIP-1b in comparison to the control group. Interestingly, HFRS patients had higher concentrations of serum MIP-1α, MIP-1β, which promote activation of macrophages and NK cells. HFRS patients had increased concentrations of IFN-γ and TNF-α, while CCHF patients had significantly higher concentrations of IFN-α and IL-8. In both, CCHF and HFRS patients’ viral load significantly correlated with IP-10. Patients with fatal outcome had significantly elevated concentrations of IL-6, IFN-α2 and MIP-1α, while GRO-α, chemokine related to activation of neutrophils and basophils, was downregulated. Our study provided a comprehensive characterization of biomarkers released in the acute stages of CCHF and HFRS.

scholarly journals A Defect in Interleukin-10 Leads to Enhanced Malarial Disease in Plasmodium chabaudi chabaudi Infection in Mice

1999 ◽  
Vol 67 (9) ◽  
pp. 4435-4442 ◽  
Author(s):  
Ching Li ◽  
Inés Corraliza ◽  
Jean Langhorne
Keyword(s):  
Body Weight ◽  
Knockout Mice ◽  
Interleukin 10 ◽  
Plasmodium Chabaudi ◽  
Double Knockout ◽  
Direct Stimulation ◽  
Necrosis Factor Alpha ◽  
Glucose Levels ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Infection of interleukin-10 (IL-10)-nonexpressing (IL-10−/−) mice with Plasmodium chabaudi chabaudi (AS) leads to exacerbated pathology in female mice and death in a proportion of them. Hypoglycemia, hypothermia, and loss in body weight were significantly greater in female IL-10−/−mice than in male knockout mice and all wild-type (WT) mice during the acute phase of infection. At this time, both female and male IL-10−/− mice produced more gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-12p40 mRNA than their respective WT counterparts. Inactivation of IFN-γ in IL-10−/− mice by the injection of anti-IFN-γ antibodies or by the generation of IL-10−/− IFN-γ receptor−/− double-knockout mice resulted in reduced mortality but did not affect body weight, temperature, or blood glucose levels. The data suggest that IFN-γ-independent pathways may be responsible for these pathological features of P. chabaudimalaria and may be due to direct stimulation of TNF-α by the parasite. Since male and female knockout mice both produce more inflammatory cytokines than their WT counterparts, it is likely that the mortality seen in females is due to the nature or magnitude of the response to these cytokines rather than the amount of IFN-γ or TNF-α produced.

scholarly journals Clinical and Immunologic Features of an Atypical Intracranial Mycobacterium avium Complex (MAC) Infection Compared with Those of Pulmonary MAC Infections

2008 ◽  
Vol 15 (10) ◽  
pp. 1580-1589 ◽  
Author(s):  
Mouhannad Sadek ◽  
Feng Yun Yue ◽  
Erika Yue Lee ◽  
Gabor Gyenes ◽  
R. Brad Jones ◽  
...  
Keyword(s):  
T Cell ◽  
Mycobacterium Avium ◽  
The Body ◽  
Interleukin 12 ◽  
Elderly Persons ◽  
Necrosis Factor Alpha ◽  
Healthy Elderly ◽  
Tnf Α ◽  
Ifn Γ ◽  
The Individual

ABSTRACT Members of the Mycobacterium avium complex (MAC) may cause chronic pulmonary infections in otherwise healthy elderly persons but rarely invade parts of the body outside of the lungs in immunocompetent hosts. We present a case of an isolated intracranial MAC infection in an apparently immunocompetent individual and review previous reports. We studied the T-cell and monocyte responses in healthy volunteers, individuals with a pulmonary MAC infection, and one individual with an isolated intracranial MAC infection. Genomic DNA from the individual with the brain MAC infection was studied for gamma interferon (IFN-γ) receptor mutations. Individuals with localized pulmonary MAC infections showed increased activation of monocytes and enhanced monocyte and T-cell tumor necrosis factor alpha (TNF-α) production in response to lipopolysaccharide and MAC antigens but defects in T-cell IFN-γ secretion. The individual with an intracranial MAC infection showed a lack of monocyte activation and deficiencies in both monocyte and T-cell TNF-α production and monocyte interleukin-12 (IL-12) production but had preserved T-cell IFN-γ production. Mutations or deletions in the IFN-γ receptor were not detected in the individual with the intracranial MAC infection. Our data suggest that distinct immune defects characterize two different manifestations of MAC infection. A relative defect in IFN-γ production in response to MAC may predispose an individual to localized but partially controlled lung disease, whereas defects leading to reduced IL-12 and TNF-α production may allow the dissemination of MAC. Further studies delineating the potential role of TNF-α in limiting the spread of MAC outside the lung are warranted.

Clinical, Virological, and Immunological Profiles of DENV, ZIKV, and/or CHIKV-Infected Brazilian Patients

Intervirology ◽  
2020 ◽  
Vol 63 (1-6) ◽  
pp. 33-45
Author(s):  
Juan Camilo Sánchez-Arcila ◽  
Jessica Badolato-Correa ◽  
Thiara Manuele Alves de Souza ◽  
Iury Amâncio Paiva ◽  
Luciana Santos Barbosa ◽  
...  
Keyword(s):  
Viral Load ◽  
Inverse Correlation ◽  
Interleukin 10 ◽  
Serum Samples ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Infected Adult ◽  
Chemokine Ligand ◽  
And Migration

<b><i>Background:</i></b> Arboviruses co-circulating within a population that are transmitted by the same vector have the potential to cause coinfections. Coinfections with dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) have been occurring in Brazil, but it is not well-understood how human responses vary during mono- or coinfections and whether they play different roles in pathogenesis. <b><i>Methods:</i></b> We investigated the clinical, virological, and immunological status during patients’ acute infections, focusing on the CCL/CXC chemokines, proinflammatory, as well as anti-inflammatory cytokines levels quantified by ELISAs. Viral load was determined by qRT-PCR in serum samples from 116 acute DENV, ZIKV, CHIKV, DENV/ZIKV, and CHIKV/ZIKV-infected adult patients from Brazil. <b><i>Results:</i></b> Most of the acute patients displayed fever, headache, prostration, and myalgia, regardless of the type of arbovirus infection. Zika viral load was higher in CHIKV/ZIKV coinfected patients compared with ZIKV or DENV/ZIKV infections. All infected individuals presented increased concentrations of C-X-C motif chemokine ligand 10/interferon protein-10 (CXCL10/IP-10), C-C motif chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1), and tumor necrosis factor alpha (TNF-α) compared to healthy donors. Interestingly, the ZIKV group separated from CHIKV/ZIKV due to higher levels of interleukin-10 (IL-10) and lower levels of TNF-α. While DENV/ZIKV differentiated from CHIKV due to their higher levels of CCL2/MCP-1, in CHIKV- and CHIKV/ZIKV-infected patients, levels of CXC10/IP-10, CCL2/MCP-1, and migration inhibitory factor (MIF) were associated with CHIKV viral load. By contrast, in DENV/ZIKV- and CHIKV/ZIKV-infected patients, levels of CXCL10/IP-10, CCL2/MCP-1, and TNF-α showed a significant inverse correlation with ZIKV viral load. <b><i>Conclusions:</i></b> From all the circulating mediators measured, we detected differences of IL-10, TNF-α, and CCL2/MCP-1 between arbovirus groups. We hypothesize that CXC10/IP-10, CCL2/MCP-1, and MIF in the CHIKV-infected group could regulate the CHIKV viral load, while CXC10/IP-10, CCL2/MCP-1, and TNF-α in DENV/ZIKV, and CHIKV/ZIKV groups, could regulate ZIKV viral load.

scholarly journals Autocrine and Exocrine Regulation of Interleukin-10 Production in THP-1 Cells Stimulated with Borrelia burgdorferi Lipoproteins

2002 ◽  
Vol 70 (4) ◽  
pp. 1881-1888 ◽  
Author(s):  
Guillermo H. Giambartolomei ◽  
Vida A. Dennis ◽  
Barbara L. Lasater ◽  
P. K. Murthy ◽  
Mario T. Philipp
Keyword(s):  
Borrelia Burgdorferi ◽  
Interleukin 10 ◽  
Feedback Mechanism ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Necrosis Factor Alpha ◽  
Negative Feedback Mechanism ◽  
Human Monocytic Cell Line ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT We have recently demonstrated that interleukin-10 (IL-10), produced by THP-1 monocytes in response to Borrelia burgdorferi lipoproteins, dampens the production of concomitantly elicited inflammatory cytokines. Thus, IL-10 could potentially down-regulate inflammatory and microbicidal effector mechanisms of the innate immune response to a B. burgdorferi infection, facilitating the establishment of the spirochete. To understand the mechanism(s) implicated in the regulation of the synthesis and release of IL-10 during early infection, we investigated the autocrine effects of IL-6, IL-12, tumor necrosis factor alpha (TNF-α), and IL-10 itself, as well as the exocrine effect of IFN-γ on the production of macrophage-derived IL-10 with lipoprotein as a stimulant. In addition, in view of the differences in the receptor and signal transduction pathways of lipopolysaccharide (LPS) and bacterial lipoproteins, we also investigated the effects described above with LPS as a stimulant. The THP-1 human monocytic cell line and purified recombinant lipidated OspA (L-OspA) were used as the model target cell and stimulant, respectively. TNF-α increased the production of IL-10, as elicited by lipoproteins. The production of IL-10 by THP-1 cells stimulated with L-OspA was autoregulated by a negative feedback mechanism involving the IL-10 receptor (IL-10R). Exogenous IFN-γ significantly inhibited the production of IL-10. Both autocrine (IL-10) and exocrine (IFN-γ) inhibition of IL-10 production resulted in an increase in the production of the proinflammatory cytokines IL-6 and IL-12. The same results were obtained when the stimulant was LPS. The results further illustrate that IL-10 may play a pivotal role in Lyme disease pathogenesis. Moreover, the regulation of its production with lipoprotein as a stimulant is indistinguishable from that observed when LPS acts as a stimulant.

scholarly journals Serum Interleukin Profile in Patients with Graves Orbithopathy

2013 ◽  
Vol 59 (1) ◽  
pp. 31-35
Author(s):  
Zsuzsánna Réti ◽  
Iz Kun ◽  
Corina Cristina Radu Pop
Keyword(s):  
Disease Activity ◽  
Interleukin 1 ◽  
Interleukin 2 ◽  
Interleukin 10 ◽  
Interleukin 4 ◽  
Disease Stage ◽  
Clinical Activity ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

Abstract Background: Graves’ orbitopathy (GO) is considered an autoimmune condition in close relationship with Graves’ disease (GD) affecting the thyroid. Several similarities exist between the two conditions, sharing the common antigen and the characteristics of the inflammation mediated by a number of cytokines. The result of the immune reactions will lead to the expansion of adipose tissue, production of glycosaminoglycans and soft tissue inflammation. Material and methods: In our study we examined the serum level of interleukin-1 (IL-1), interleukin 2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) in correlation with the activity of disease and smoking habits in 25 patients with GD and GO. Results: We found that smokers had higher serum IL-6 and lower serum MCP-1, IL-8 and TNF-α level compared to non-smokers. Also, we found a weak positive correlation between serum IL-10, IFN-γ and disease activity (clinical activity score, CAS) and negative correlation between serum IL-1 and activity. Conclusion: Our findings support the fact that some cytokines (IL-10, IFN-γ, IL-1) play a role in active disease, while others are influenced by environmental factors, such as smoking (IL-6, IL-8, TNF-α). The discrepancy of cytokine profiles may reflect different patient characteristics, such as disease stage and disease activity and determination of serum cytokines would be useful in selecting patients who need more aggressive treatment protocols.

scholarly journals Pathology of Plasmodium chabaudi chabaudi Infection and Mortality in Interleukin-10-Deficient Mice Are Ameliorated by Anti-Tumor Necrosis Factor Alpha and Exacerbated by Anti-Transforming Growth Factor β Antibodies

2003 ◽  
Vol 71 (9) ◽  
pp. 4850-4856 ◽  
Author(s):  
Ching Li ◽  
Latifu A. Sanni ◽  
Fakhreldin Omer ◽  
Eleanor Riley ◽  
Jean Langhorne
Keyword(s):  
Tumor Necrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Plasmodium Chabaudi ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Interleukin-10 (IL-10)-deficient (IL-10−/−) mice infected with Plasmodium chabaudi (AS) suffer a more severe disease and exhibit a higher rate of mortality than control C57BL/6 mice. Here, we show that a drop in body temperature to below 28°C and pronounced hypoglycemia of below 3 mM are reliable indicators of a lethal infection. Elevated inflammatory responses have been shown to accompany pathology in infected IL-10−/− mice. We show that neutralization of tumor necrosis factor alpha (TNF-α) in IL-10−/− mice abolishes mortality and ameliorates the hypothermia, weight loss, and anemia but does not affect the degree of hypoglycemia. These data suggest that TNF-α is involved in some of the pathology associated with a P. chabaudi infection in IL-10−/− mice but other factors play a role. IL-10−/− mice that survive a primary infection have been shown to control gamma interferon (IFN-γ) and TNF-α production, indicating that other cytokines or mechanisms may be involved in their down-regulation. Significantly higher levels of transforming growth factor β (TGF-β), a cytokine with such properties, are present in the plasma of infected IL-10−/− mice at a time that coincides with the disappearance of IFN-γ and TNF-α from the blood. Neutralization of TGF-β in IL-10−/− mice resulted in higher circulating amounts of TNF-α and IFN-γ, and all treated IL-10−/− mice died within 12 days with increased pathology but with no obvious increase in parasitemia. Our data suggest that a tight regulation of the balance between regulatory cytokines such as IL-10 and TGF-β and inflammatory cytokines such as IFN-γ and TNF-α is critical for survival in a mouse malaria infection.

scholarly journals The Contraceptive Depot Medroxyprogesterone Acetate Impairs Mycobacterial Control and Inhibits Cytokine Secretion in Mice Infected with Mycobacterium tuberculosis

2013 ◽  
Vol 81 (4) ◽  
pp. 1234-1244 ◽  
Author(s):  
Léanie Kleynhans ◽  
Nelita Du Plessis ◽  
Nasiema Allie ◽  
Muazzam Jacobs ◽  
Martin Kidd ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Medroxyprogesterone Acetate ◽  
Bacterial Load ◽  
Interleukin 10 ◽  
Colony Stimulating Factor ◽  
Necrosis Factor Alpha ◽  
Depot Medroxyprogesterone Acetate ◽  
Tnf Α ◽  
Ifn Γ ◽  
Stimulating Factor

ABSTRACTThe contraceptive depot medroxyprogesterone acetate (DMPA), with progestin as the single active compound, possesses selective glucocorticoid activity and can alter the expression of glucocorticoid receptor-regulated genes. We therefore propose that pharmacological doses of DMPA used for endocrine therapy could have significant immune modulatory effects and impact on susceptibility to, as well as clinical manifestation and outcome of, infectious diseases. We investigated the effect of contraceptive doses of DMPA in two different murineMycobacterium tuberculosismodels. Multiplex bead array analysis revealed that DMPA altered serum cytokine levels of tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), and interleukin 10 (IL-10) in C57BL/6 mice and gamma interferon (IFN-γ) in BALB/c mice. DMPA also suppressed antigen-specific production of TNF-α, G-CSF, IL-10, and IL-6 and induced the production of IP-10 in C57BL/6 mice. In BALB/c mice, DMPA altered the antigen-specific secretion of IFN-γ, IL-17, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and monocyte chemotactic protein 1 (MCP-1). Furthermore, we show that C57BL/6 mice treated with doses of DMPA, which result in serum concentrations similar to those observed in contraceptive users, have a significantly higher bacterial load in their lungs. Our data show for the first time that DMPA impacts tuberculosis (TB) disease severity in a mouse model and that the effects of this contraceptive are not confined to infections of the genital tract. This could have major implications for the contraceptive policies not only in developing countries like South Africa but also worldwide.

scholarly journals Cytokine mRNA Expression in Mycobacteriam ulcerans-Infected Human Skin and Correlation with Local Inflammatory Response

2006 ◽  
Vol 74 (5) ◽  
pp. 2917-2924 ◽  
Author(s):  
R. Phillips ◽  
C. Horsfield ◽  
J. Mangan ◽  
K. Laing ◽  
S. Etuaful ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Interleukin 10 ◽  
Mycobacterium Ulcerans ◽  
Cytokine Mrna ◽  
Necrosis Factor Alpha ◽  
Tissue Samples ◽  
Local Inflammatory Response ◽  
Cytokine Mrna Expression ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Cytokine mRNA expression in biopsies of Mycobacterium ulcerans-infected human tissue was investigated using real-time PCR, and the findings were correlated with the clinical stages of disease and histopathologies. A broad range of cytokine mRNAs were detected in 16 early nodules and 28 late-stage ulcers, including those for the Th1 cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) and the Th2 cytokine interleukin 10 (IL-10). IFN-γ was strongly expressed in both nodules and ulcers, suggesting that a Th1 response begins early in the disease. There was a significantly higher expression of IL-8 and other proinflammatory cytokines in results from 32 biopsies with neutrophilia than in those from 12 biopsies without acute inflammation. Ten tissue samples containing granulomas showed high mRNA expression for IFN-γ, IL-1β, IL-12p35, IL-12p40, IL-15, and TNF-α relative to 34 tissue samples without granulomas. These results suggest that the human immune response to M. ulcerans is similar to that seen with some other mycobacteria despite the presence of the toxin mycolactone in the tissues.

scholarly journals Tumor Necrosis Factor Alpha-Mediated Toxic Shock inTrypanosoma cruzi-Infected Interleukin 10-Deficient Mice

2000 ◽  
Vol 68 (7) ◽  
pp. 4075-4083 ◽  
Author(s):  
Christoph Hölscher ◽  
Markus Mohrs ◽  
Wen Juan Dai ◽  
Gabriele Köhler ◽  
Bernhard Ryffel ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 10 ◽  
Toxic Shock ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

ABSTRACT Using interleukin-10 (IL-10)-deficient (IL-10−/−) mice, previous studies revealed a pathological immune response after infection with Trypanosoma cruzi that is associated with CD4+ T cells and overproduction of proinflammatory cytokines. In this study we further investigate the pathology and potential mediators for the mortality in infected animals. T. cruzi-infected IL-10−/− mice showed reduced parasitemia accompanied by increased systemic release of gamma interferon (IFN-γ), IL-12, and reactive nitrogen intermediates and overproduction of tumor necrosis factor alpha (TNF-α). Despite this early resistance, IL-10−/− mice died within the third week of infection, whereas all control mice survived acute infection. The clinical manifestation with weight loss, hypothermia, hypoglycemia, hyperkalemia, and increased liver-derived enzymes in the blood together with hepatic necrosis and intravascular coagulation in moribund mice indicated a toxic shock-like syndrome, possibly mediated by the systemic TNF-α overproduction. Indeed, high production of systemic TNF-α significantly correlated with mortality, and moribund mice died with critically high TNF-α concentrations in the blood. Consequent treatment with anti-TNF-α antiserum attenuated pathological changes in T. cruzi-infected IL-10−/− mice and significantly prolonged survival; the mice died during the fourth week postinfection, again with a striking correlation between regaining high systemic TNF-α concentrations and the time of death. Since elevated serum IL-12 and IFN-γ concentrations were not affected by the administration of antiserum, these studies suggest that TNF-α is the direct mediator of this toxic shock syndrome. In conclusion, induction of endogenous IL-10 during experimentally induced Chagas' disease seems to be crucial for counterregulating an overshooting proinflammatory cytokine response resulting in TNF-α-mediated toxic shock.

Sign in / Sign up

Export Citation Format

Share Document