interleukin-8 and Leishmaniasis--Visceral

The Ibizan Hound is a canine breed native to the Mediterranean region, where leishmaniasis is an endemic zoonosis. Several studies indicate a low prevalence of this disease in Ibizan Hound dogs, whereas other canine breeds present a high prevalence. However, the underlying molecular mechanisms still remain unknown. The aim of this work is to analyse the relationship between serum levels of cytokines and the genomic profiles in two canine breeds, Ibizan Hound (resistant canine breed model) and Boxer (susceptible canine breed model).. In this study, we analyse the haplotypes of genes encoding cytokines related to immune response of Leishmania infantum infection in twenty-four Boxers and twenty-eight Ibizan Hounds apparently healthy using CanineHD DNA Analysis BeadChip including 165,480 mapped positions. The haplo.glm extension of haplo.score was used to perform a General Linear Model (GLM) regression to estimate the magnitude of individual haplotype effects within each cytokine.. Mean levels of interferon gamma (IFN-γ), interleukin 2 (IL-2) and IL-18 in Boxer dogs were 0.19 ± 0.05 ng/ml, 46.70 ± 4.54 ng/ml, and 36.37 ± 30.59 pg/ml, whereas Ibizan Hound dogs present 0.49 ± 0.05 ng/ml, 64.55 ± 4.54 ng/ml, and 492.10 ± 31.18 pg/ml, respectively. The GLM regression shows fifteen haplotypes with statistically significant effect on the cytokine serum levels (P < 0.05). The more relevant are IL6-CGAAG and IFNG-GCA haplotypes, which increase and decrease the IL-2, IL-8 and IFN-γ serum levels, respectively.. Haplotypes in the IFNG and IL6 genes have been correlated to serum levels of IFN-γ, IL-2 and IL-18, and a moderate effect has been found on IL8 haplotype correlated to IL-8 and IL-18 serum levels. The results indicate that the resistance to L. infantum infection could be a consequence of certain haplotypes with a high frequency in the Ibizan Hound dog breed, while susceptibility to the disease would be related to other specific haplotypes, with high frequency in Boxer. Future studies are needed to elucidate whether these differences and haplotypes are related to different phenotypes in immune response and expression gene regulation to L. infantum infections in dogs and their possible application in new treatments and vaccines.

Topics: Animals; Cytokines; Dog Diseases; Dogs; Haplotypes; Interferon-gamma; Interleukin-18; Interleukin-2; Interleukin-6; Interleukin-8; Leishmania infantum; Leishmaniasis; Leishmaniasis, Visceral

Early biomarkers of the response to treatment are lacking and may help to reduce mortality by the vector-borne disease visceral leishmaniasis (VL).. A prospective cohort study was conducted to investigate plasma cytokines and clinical laboratory data as biomarkers of the early response to specific treatment for VL in 36 patients.. The mean interleukin 6 (IL-6) concentration on the 7th day was 2.3% of the pre-treatment concentration, interleukin 10 (IL-10) was 8.0%, and interleukin 8 (IL-8) was 8.2%. On the 7th day, IL-10 was below half of the pre-treatment concentration in 100.0%, IL-8 in 95.5% and IL-6 in 90.9%. The spleen and liver sizes, haemoglobin, interleukin 1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α) showed a slower recovery. Fever disappeared in 91% on the 7th day, 69.4% had a normal white cell count, and 77.8% had a normal platelet value by this time.. The plasma cytokines IL-6, IL-10 and IL-8 were demonstrated to be excellent markers of the early response to VL treatment and if tested before the 7th day, will likely prove to be better than fever measurement.

Topics: Biomarkers; Cytokines; Female; Humans; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Leishmaniasis, Visceral; Male; Prospective Studies; Spleen; Treatment Outcome; Tumor Necrosis Factor-alpha

Visceral leishmaniasis is a chronic disease that affects humans and dogs as well. Dogs, the domestic reservoir of Leishmania, play a central role in the transmission of visceral leishmaniasis, the most severe form of this disease. Neutrophils are the most abundant leukocytes in blood and interact with the parasite after infection. Here, we evaluate the effector properties of neutrophils from healthy and naturally Leishmania infantum-infected dogs. Our results showed that the parasite induced neutrophil extracellular trap (NET) release from neutrophils in both groups. Additionally, phagocytosis and NETs contributed differently to parasite killing by neutrophils from healthy and infected animals, and IFN-γ, IL-8, IL-4 and TNF-α production by neutrophils from both groups were differentially modulated by the parasite. Our results contribute to a better understanding of the complex role played by neutrophils in canine visceral leishmaniasis, which may favor the development of more effective therapies.

Topics: Animals; Dog Diseases; Dogs; Extracellular Traps; Female; Interferon-gamma; Interleukin-4; Interleukin-8; Leishmania infantum; Leishmaniasis, Visceral; Male; Neutrophils; Phagocytosis; Tumor Necrosis Factor-alpha

Interleukin (IL)-8 plays important roles in the recruitment and activation of immune cells during visceral leishmaniasis (VL). Genetic variations in IL-8 modulate the expression of IL-8 protein and may be associated with VL. This study aimed to evaluate polymorphisms at the IL-8 -251 position in VL patients.. This cross-sectional study was performed on three groups: Leishmania-seropositive patients with clinical symptoms of VL (n = 91), seropositive patients without clinical symptoms (n = 104), and healthy controls (n = 110). Polymorphisms at the IL-8-251 position were analyzed using allele-specific polymerase chain reaction (PCR). Anti-Leishmania antibody titers were assessed by immunofluorescence.. IL-8-251 polymorphism was significantly associated with VL (P<0.002). The IL-8-251 T/T genotype was significantly higher in group 1 than in groups 2 and 3 (P<0.002). The validity of the data was analyzed using Hardy-Weinberg equilibrium and one-way analysis of variance (ANOVA), as well as χ2 tests.. IL-8-251 polymorphism was significantly associated with impaired immune responses in VL and might be considered a risk factor for disease development.

Topics: Alleles; Cross-Sectional Studies; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Immunity; Interleukin-8; Leishmania; Leishmaniasis, Visceral; Polymorphism, Single Nucleotide

 Leishmania infection is a cofactor in the heightened cellular activation observed in patients with American visceral leishmaniasis and human immunodeficiency virus type 1 (HIV) infection, with or without progression to AIDS (AVL/HIV). Thus, the persistence of a high parasite load despite antileishmanial therapy could be responsible for the continued immune stimulation..  CD8(+) T cells expressing CD38, parasite load, lipopolysaccharide (LPS), soluble CD14, macrophage migration inhibitory factor (MIF), intestinal fatty acid-binding protein (IFABP), and proinflammatory cytokines (interleukin 1β, interleukin 6, interleukin 8, interleukin 17, interferon γ, and tumor necrosis factor) were measured in 17 patients with AVL/HIV, 16 with HIV, and 14 healthy subjects (HS)..  Lower Leishmania parasitemia was observed after antileishmanial and antiretroviral therapies. However, higher levels of CD38(+) on CD8(+) T cells were observed in both clinical phases of leishmaniasis, compared with HIV cases. AVL/HIV and HIV patients showed higher levels of LPS and IFABP than HS. Proinflammatory cytokine levels were significantly augmented in patients with active coinfection, as well as those with remission of Leishmania infection. LPS levels and Leishmania infection were positively correlated with CD38 expression on CD8(+) T cells and with IL-6 and IL-8 levels..  LPS levels along with the immune consequences of Leishmania infection were associated with elevated cellular activation in coinfected patients. As a consequence, secondary chemoprophylaxis for leishmaniasis or even the use of antiinflammatory drugs or antibiotics may be considered for improving the prognosis of AVL/HIV.

Topics: Anti-HIV Agents; Coinfection; Cross-Sectional Studies; Fatty Acid-Binding Proteins; HIV Infections; HIV-1; Humans; Interleukin-6; Interleukin-8; Leishmaniasis, Visceral; Lipopolysaccharide Receptors; Lipopolysaccharides; Parasitemia; Real-Time Polymerase Chain Reaction

Recent clinical data suggest that severe kala-azar (or visceral leishmaniasis) is an exaggerated innate immune response mediated by inflammatory cytokines, leading to a systemic inflammatory syndrome similar to what is observed in malaria, sepsis and other diseases. We tested this hypothesis by measuring serum cytokines in individuals with kala-azar.. We compared patients with severe kala-azar (i.e. hemorrhagic manifestations, n = 38) with patients without evidence of hemorrhage (n = 96). We conducted a detailed clinical and laboratory evaluation, measuring serum IL-1beta, IL-6, IL-8, IL-10, IL-12, interferon-gamma, and TNF-alpha, and markers of disseminated intravascular coagulation (DIC).. Infants had higher levels of inflammatory cytokines, while HIV-infected patients had lower concentrations of IL-10 and interferon-gamma. Higher levels of IL-6, interferon-gamma, and IL-8 were found among deceased patients. IL-8 and interferon-gamma were independently associated with bleeding. Several cytokines were associated with different signs of severe clinical and laboratory manifestations, including DIC. IL-6 was highly positively and independently associated with IL-1beta, IL-8, IL-10, and negatively associated with TNF-alpha. IL-1beta and TNF-alpha were also highly independently associated with disease severity.. In its severe form, kala-azar, a neglected tropical disease, initiates a systemic inflammatory response that leads to DIC and other manifestations. Children may have higher risk of death due to the more intense cytokine release. The data supports the notion that IL-6 is the central cytokine that is associated with lethal disease, but interferon-gamma, IL1beta, IL-8, and TNF-alpha are also involved with disease severity. Inhibition of IL-6 is a potential target of adjuvant therapy for severe or pediatric forms of this disease.

Topics: Adolescent; Adult; Brazil; Child; Child, Preschool; Cytokines; Female; Hemorrhage; HIV Seropositivity; Humans; Infant; Inflammation Mediators; Interferon-gamma; Interleukin-10; Interleukin-12; Interleukin-1beta; Interleukin-6; Interleukin-8; Leishmaniasis, Visceral; Male; Severity of Illness Index; Tumor Necrosis Factor-alpha

The complex interplay between cytokines and chemokines regulates innate and adaptive immune responses against pathogens; specifically, cytokine and chemokine expression drives activation of immune effector cells and their recruitment to tissue infection sites. Herein, we inoculated dogs with Leishmania braziliensis antigens plus saponin (the LBSap vaccine), as well as with the vaccine components, and then used real-time PCR to evaluate the kinetics of dermal expression of mRNAs of cytokines (IL-12, IFN-γ, TNF-α, IL-4, IL-13, TGF-β and IL-10) and chemokines (CCL2, CCL4, CCL5, CCL21 and CXCL8) 1, 12, 24 and 48 h after inoculation. We also evaluated the correlation between cytokine and chemokine expression and dermal cellularity. The LBSap vaccine induced high levels of IL-12 and IL-10 expression at 12 and 24 h, respectively. Furthermore, we observed positive correlations between IL-12 and IL-13 expression, IFN-γ and IL-13 expression, and IL-13 and TGF-β expression, suggesting that a mixed cytokine microenvironment developed after immunization with the vaccine. Inoculation with the saponin adjuvant alone induced a chemokine and cytokine expression profile similar to that observed in the LBSap group. CCL4 and CXCL8 chemokine expression was up regulated by the LBSap vaccine. CCL5 expression was initially highest in the LBSap group, but at 48 h, expression was highest in the LB group. Information about the kinetics of the immune response to this vaccine gained using this dog model will help to elucidate the mechanisms of and factors involved in a protective response against Leishmania infection and will aid in establishing rational approaches for the development of vaccines against canine visceral leishmaniasis.

Topics: Animals; Chemokine CCL4; Chemokine CCL5; Chemokines; Cytokines; Dermis; Dog Diseases; Dogs; Female; Gene Expression; Host-Pathogen Interactions; Immunization; Interleukin-10; Interleukin-12; Interleukin-8; Leishmania braziliensis; Leishmaniasis Vaccines; Leishmaniasis, Visceral; Male; Reverse Transcriptase Polymerase Chain Reaction; Saponins; Time Factors

Visceral leishmaniasis (VL) or Kala-azar is a serious protozoan infectious disease caused by an obligate intracellular parasite. Cytokines have a major role in determining progression and severity of clinical manifestations in VL. We investigated polymorphisms in the TGFB1and IL8 genes, which are cytokines known to have a role in onset and severity of the disease. Polymorphisms at TGFB1 -509 C/T and +869 T/C, and IL8 -251 A/T were analyzed by a PCR-RFLP technique, in 198 patients with VL, 98 individuals with asymptomatic infection positive for a delayed-type hypersensitivity test (DTH+) and in 101 individuals with no evidence of infection (DTH-). The presence of the T allele in position -509 of the TGFB1 gene conferred a two-fold risk to develop infection both when including those with clinical symptoms (DTH+ and VL, grouped) or when considering DTH+ only, respectively p = 0.007, OR = 1.9 [1.19-3.02] and p = 0.012, OR = 2.01 [1.17-3.79], when compared with DTH- individuals. In addition, occurrence of hemorrhage was associated with TGFB1 -509 T allele. We suggest that the -509 T allele of the TGFB1 gene, a cytokine with a biologically relevant role in the natural history of the disease, may contribute to overall susceptibility to infection by Leishmania and to severity of the clinical disease.

Topics: Adolescent; Adult; Aged; Alleles; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Genotype; Humans; Infant; Interleukin-8; Leishmaniasis, Visceral; Male; Middle Aged; Transforming Growth Factor beta1

The clinical spectrum of visceral leishmaniasis (VL), a chronic intracellular parasitic disease, ranges from a subclinical, asymptomatic infection to severe clinical disease (kala-azar). In experimental leishmaniasis, mice that have a Th1 response to infection tend to have limited disease while a Th2 response is associated with disease progression. Humans with VL most often have mixed rather than polarized responses. However, most clinical studies have used methods that require a relatively large sample volume, thus limiting their scope. Measuring multiple cytokine levels in blood samples using a multiplexed microsphere assay (MMA) may be useful to further evaluate the Th1/Th2 paradigm in humans.. Bangladeshi individuals (n=120) living in an area endemic for VL were categorized into one of the five clinical categories. Sera from these individuals were measured for levels of IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-gamma, and TNF-alpha by multiplexed microsphere cytokine immunoassay.. Circulating IL-8, IL-10, and IL-12 differed significantly among the clinical groups. Persons with kala-azar demonstrated the highest median levels of IL-8 and IL-10 but lower median levels of IL-12.. The MMA for cytokines is an extremely time-and sample-efficient method for characterizing circulating cytokine levels in visceral leishmaniasis patients.

Topics: Adult; Child; Cytokines; Humans; Immunoassay; Interleukin-10; Interleukin-12; Interleukin-8; Leishmaniasis, Visceral; Microspheres