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Biomedical subjects

E M Carvalho

Publications and source records attributed to E M Carvalho.

At least 37 records · Page 2Linked to original sources
PubMed2001

Influence of human T-cell lymphocytotropic virus type 1 infection on serologic and skin tests for strongyloidiasis.

The aim of this study was to determine whether human T-cell lymphocytotropic virus type 1 (HTLV-1) infection may affect the levels of parasite-specific immunoglobulin (Ig) G and IgE and the positivity of the skin test for strongyloidiasis. Participants included 67 patients with strongyloidiasis (40 without HTLV-1 infection and 27 coinfected with HTLV-1). We determined IgG and IgE levels by enzyme-linked immunosorbent assay, and the immediate hypersensitivity skin test was performed with the metabolic Strongyloides stercoralis antigen. Specific IgE levels and the size of skin reactions in patients without HTLV-1 were higher (P < 0.01) than those observed in patients coinfected with HTLV-1. Additionally, 89% of patients without HTLV-1 had specific IgE and 92.5% had positive skin tests; however, these values were significantly reduced (P < 0.01) in patients coinfected with HTLV-1 (44% and 59%, respectively). These data show that HTLV-1 infection decreases the sensitivity of detection of S. stercoralis-specific IgE, the size of the immediate hypersensitivity reaction, and the sensitivity of these tests in the diagnosis of strongyloidiasis.

Adult↗
PubMed2001

Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony.

Mucosal leishmaniasis is characterized by an intense inflammatory reaction and tissue damage with few parasites in the lesion. On the basis of previous observations that suggest a possible role of tumor necrosis factor alpha (TNF-alpha) in the pathology of this disease, an open-label study was performed to evaluate the efficacy of the treatment with an inhibitor of TNF-alpha (pentoxifylline) associated to antimony therapy in 10 patients with refractory mucosal leishmaniasis. Patients were treated with pentavalent antimony (20 mg per kilogram of body weight per day) plus orally administered pentoxifylline 400 mg 3 times daily for 30 days. Nine of 10 patients fulfilled the criteria for cure: they experienced complete reepithelization of the mucosal tissue 90 days after therapy and displayed no evidence of relapse at 1 year of follow-up. The TNF-alpha levels before therapy (776 +/- 342 pg/mL) fell to 94 +/- 57 pg/mL (P < 0.05) within 60 days after therapy. Our results indicate that pentoxifylline plus antimony therapy should be considered in all patients with mucosal leishmaniasis that is refractory to treatment.

Administration, Oral↗
PubMed2000

IL-10 and IL-12 are the main regulatory cytokines in visceral leishmaniasis.

Visceral leishmaniasis (VL) is characterized by the absence of cytokines such as IFN-gamma and IL-12. Cure of VL is associated with a restoration of the ability to make these cytokines. The aim of the present study was to evaluate the role of IL-12 in the recovery of the ability to produce IFN-gamma and to test whether or not IL-4 IL-10 and/or TGF-beta could suppress IFN-gamma production by PBMC from treated VL patients. High stimulation index (SI) of proliferation was observed in PBMC from subjects stimulated with Leishmania chagasi antigen (181+/-83). Neutralizing IL-12 inhibited lymphoproliferation [stimulation index (SI) of 210+/-114 to 1+/-0.6 (P<0.01)] and/or the production of IFN-gamma [2792+/-402 pg/ml to 407+/-449 pg/ml (P<0.01)]. Recombinant IL-10 abrogated the lymphoproliferation (SI=2+/-3) while recombinant IL-4 or TGF-beta had no effect on this response (147+/-22 and 194+/-12 respectively). IFN-gamma was high when PBMCs were stimulated with L. chagasi (873+/-400 pg/ml) and this was abrogated by the addition of IL-10 (5+/-2 pg/ml). In contrast neither IL-4 or TGF-beta suppressed IFN-gamma production (837+/-244 pg/ml and 759+/-523 pg/ml). These results indicate that IL-12 plays an important role in the ability of treated VL patients to make IFN-gamma and that IL-10 but not IL-4 or TGF-beta inhibits this response.

Antibodies↗
PubMed2000

Human immune responses to Schistosoma mansoni vaccine candidate antigens.

To determine the naturally occurring immunological responses to the Schistosoma mansoni antigens paramyosin, IrV-5, Sm-23 (MAP-3), and triose phosphate isomerase (MAP-4), a total of 119 subjects from an area of endemicity for schistosomiasis, including "resistant" subjects (n = 17) were evaluated. Specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, and IgA levels for each of the antigens and the cytokine profile in culture supernatants from antigen-stimulated peripheral blood mononuclear cells (PBMC) were determined. Although all the subjects had a high degree of contaminated water exposure, their infection levels were variable (0 to 1,128 eggs/g of stool). There were direct correlations between infection levels and levels of SWAP- and paramyosin-specific IgG1 and IgG4 (P < 0.05). However, an inverse correlation between infection levels and specific IgG2 to IrV-5 (P < 0.01) was observed. The evaluation of the cytokine profile (interleukin 5 [IL-5], IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha) in response to these antigens showed inverse correlations between the degree of infection and IFN-gamma levels in PBMC supernatants stimulated with paramyosin (P < 0.05) and IrV-5 (P < 0.01). Additionally, inverse correlations between the degree of infection and IL-5 levels in MAP-3- and MAP-4-stimulated PBMC supernatants (P < 0.01) were found. Logistic regression analysis was performed to adjust the results of cytokine profile by age. IL-5 production in MAP-3-stimulated PBMC supernatants was associated with lower infection levels (odds ratio = 11.2 [95% confidence interval, 2.7 to 45.8]).

Adult↗
PubMed2000

Inverse association between skin response to aeroallergens and Schistosoma mansoni infection.

BACKGROUND: Helminthic infections and allergic disease are highly prevalent in many areas of the world. It is known that IgE antibodies are involved in the pathogenesis of both helminthiasis and atopy. However, the consequences of the presence of helminthic infections in atopic patients are still not completely understood. METHODS: Subjects infected by Schistosoma mansoni with more than 200 eggs/g of feces (n = 42) and uninfected subjects (n = 133) were selected from an endemic area of schistosomiasis. The history of allergy and results of the immediate hypersensitivity prick tests with inhalant allergen extracts were registered. Total IgE and IgE specific to S. mansoni and aeroallergens were measured in serum by ELISA. RESULTS: The proportion of individuals with a positive skin test to allergens was higher in the uninfected group (24.3%) than in the group with more than 200 eggs/g of feces (4.8%). The odds of atopy (defined as a positive test for at least one of the antigens) were 5 times higher (odds ratio = 7.0; 95% confidence interval = 1.6-31.1%; p = 0.01) in the uninfected group, after taking into account the potential influence of gender and age. While there was a tendency for higher total and S. mansoni-specific IgE levels in infected patients, an opposite trend, that is higher aeroallergen-specific IgE, was observed in uninfected subjects. CONCLUSIONS: There was a strong and statistically significant inverse association between the immediate skin test response to common aeroallergens and infection by S. mansoni. The results indicate that immediate hypersensitivity reactions may be suppressed in S. mansoni-infected individuals.

Adolescent↗
PubMed2000

Mucosal leishmaniasis: quantitative nasal cytology as a marker of disease activity and indicator of healing.

Mucosal leishmaniasis (ML) follow-up is based on subjective parameters. Using simplified quantitative cytology of nasal lavages (QNCs), we studied 20 ML patients, 10 patients with cutaneous leishmaniasis (CL), and 10 healthy subjects. Patients with ML were treated with antimony and followed up with otolaryngological examination plus QNCs for 6 months. At the first evaluation, the median total number of cells in ML patients (1,540,000) was greater than that in CL patients (215,000) or that in healthy subjects (250,000). Neutrophils were predominant in ML patients, in contrast to both sets of controls, in whom epithelial cells were more frequent. During treatment, we found a significant reduction in total nasal cell counts in ML patients who were cured, and encountered a switch in predominant cell type. The cytology of 2 patients who did not respond to antimony remained the same. It is therefore possible to detect nasal inflammation in ML patients through QNCs, which may indicate extension of mucosal involvement, providing an objective parameter to monitor therapy.

Adolescent↗
PubMed1999

Immunochemotherapy with interferon-gamma and multidrug therapy for multibacillary leprosy.

Treatment for multibacillary leprosy is presently performed with a multidrug therapy (MDT) scheme maintained for 2 years. Leprosy treatment however can benefit from the reduction of length. The lack of interferon-gamma (IFN-gamma) production by lepromatous leprosy (LL) patients' lymphocytes lead us to use this cytokine in the treatment of multibacillary leprosy associated with MDT in the treatment of multibacillary leprosy, and monitor several clinical and immunological parameters during the course of treatment. A total of 20 multibacillary leprosy patients were evaluated, 10 treated with MDT alone, and 10 treated with MDT + 10 daily doses of 2 x 10(6) international units (IU) of recombinant human IFN-gamma/m2 followed by 10 daily doses of 10(7) IU IFN-gamma/m2, intramuscularly, during the first 20 days of MDT. IFN-gamma was well tolerated and did not cause any increase in the rate of leprosy reactions development during treatment. Decrease of bacillary load, fall of anti-Mycobacterium leprae IgG serum antibodies, changes of histological pattern, as well as changes in lymphocyte proliferation assay in response to mitogens (PHA or PWM), M. leprae antigen or PPD was similar in both groups of patients. Among several soluble immunological markers measured before and 30 days after beginning of treatment, levels of soluble IL-2R receptor increased in patients treated with MDT plus IFN-gamma whereas decreased in patients treated with MDT alone. Soluble ICAM-1 levels decreased in the MDT group but did not change in the MDT + IFN-gamma treated patients. Soluble CD4 and soluble CD8 markers did not change significantly in either group of patients. Neopterin, a marker of macrophage activation, increased in all but one patient treated with MDT + IFN-gamma but in none treated with MDT alone, indicating that IFN-gamma was active in vivo. Our findings indicate that despite being able to promote macrophage activation in multibacillary leprosy patients a short course of systemically administered IFN-gamma is not able to change the clinical course of a long standing disease such as leprosy.

Adolescent↗
PubMed1999

Down-regulation of Th1 type of response in early human American cutaneous leishmaniasis.

This study examined the T cell responses in the early phase of Leishmania braziliensis infection. Cytokine profiles, lymphoproliferative responses, and skin test results in 25 patients with early cutaneous leishmaniasis (ECL; illness duration <60 days) were compared with those in persons with late cutaneous leishmaniasis (LCL; illness duration >2 months). Absent or low lymphoproliferative responses were observed in 8 (32%) of 25 patients and an absence of interferon (IFN)-gamma production in 9 (41%) of 22 patients prior to therapy. IFN-gamma production in ECL (mean +/- SD) was lower than in LCL (293+/-346 vs. 747+/-377 pg/mL, respectively; P<.01). In contrast, interleukin (IL)-10 production in ECL (mean +/- SD) was higher than in LCL (246+/-56 vs. 50+/-41 pg/mL, respectively; P<.01). Restoration of lymphoproliferative responses and IFN-gamma production was achieved when monoclonal antibody to IL-10 or IL-12 was added to the cultures. These results show that T cell responses during early-phase infection are down-regulated by IL-10 and may facilitate parasite multiplication.

Animals↗
PubMed1999

Randomized, double-blind study of stibogluconate plus human granulocyte macrophage colony-stimulating factor versus stibogluconate alone in the treatment of cutaneous Leishmaniasis.

The response to recombinant human granulocyte macrophage colony-stimulating factor (GM-CSF) in the treatment of cutaneous leishmaniasis was evaluated. Twenty patients with cutaneous leishmaniasis who had lesions for 60 days were enrolled in a double-blind placebo trial of GM-CSF with standard parenteral sodium stibogluconate (20 mg/kg-1/day-1) for 20 days. Ten patients were randomized to receive intralesionally injected GM-CSF (200 microgram) at enrollment and 1 week after, and 10 patients received saline as placebo. GM-CSF- and antimony-treated patients healed faster than patients who received antimony alone (49+/-32.8 vs. 110+/-61.6 days, P<.05). Seven of 10 patients were healed of their lesions before 40 days after therapy in the GM-CSF group, compared with only 1 of 10 patients in the placebo group (relative risk, 7; 95% confidence interval, 1.04-47.00). Thus, GM-CSF plus antimony significantly increased the chance of lesion healing in 40 days.

Adolescent↗
PubMed1999

Detection of specific IgE antibodies in parasite diseases.

Activation of Th1 or Th2 cells is associated with production of specific immunoglobulin isotypes, offering the opportunity to use antibody measurement for evaluation of T cell function. Schistosomiasis and visceral leishmaniasis are diseases associated with Th2 activation. However, an IgE response is not always detected in these patients. In the present study we evaluated specific IgE antibodies to S. mansoni and L. chagasi antigens by ELISA after depletion of serum IgG with protein G immobilized on Sepharose beads or RF-absorbent (purified sheep IgG antibodies anti-human IgG). In schistosomiasis patients, specific IgE to SWAP antigen was demonstrable in only 10 of 21 patients (48%) (mean absorbance +/- SD = 0.102 +/- 0.195) when unabsorbed serum was used. Depletion of IgG with protein G increased the number of specific IgE-positive tests to 13 (62%) and the use of RF-absorbent increased the number of positive results to 20 (95%) (mean absorbances +/- SD = 0.303 +/- 0. 455 and 0.374 +/- 0.477, respectively). Specific IgE anti-L. chagasi antibodies were not detected in unabsorbed serum from visceral leishmaniasis patients. When IgG was depleted with protein G, IgE antibodies were detected in only 3 (11%) of 27 patients, and the use of RF-absorbent permitted the detection of this isotype in all 27 visceral leishmaniasis sera tested (mean absorbance +/- SD = 0.104 +/- 0.03). These data show that the presence of IgG antibodies may prevent the detection of a specific IgE response in these parasite diseases. RF-absorbent, a reagent that blocks IgG-binding sites and also removes rheumatoid factor, was more efficient than protein G for the demonstration of specific IgE antibodies.

Animals↗
PubMed1998

Interferon-gamma and interleukin-4 responses in relation to serum IgE levels in persons infected with human T lymphotropic virus type I and Strongyloides stercoralis.

Possible immunologic interaction between infection with human T lymphotropic virus type 1 (HTLV-1), a retrovirus, and the intestinal parasite Strongyloides stercoralis was investigated in persons infected with one or both agents. This was done by examining the cytokine responses of peripheral blood mononuclear cells (PBMC) to mitogens and Strongyloides antigen. PBMC of subjects infected with HTLV-1 spontaneously produced interferon (IFN)-gamma with levels that correlated inversely with serum IgE levels. HTLV-1-infected subjects also had poor interleukin (IL)-4 responses to mitogenic stimulation, unlike persons without HTLV-1 infection. It is postulated that the IFN-gamma produced by activated T cells in some HTLV-1-infected persons acts to down-regulate IL-4 with consequent reduction of serum IgE levels. The impaired IgE responses and other effects of IL-4 down-regulation may be contributing factors to more severe disease and impaired response to treatment of strongyloidiasis in some HTLV-1-infected persons.

Animals↗
PubMed1998

Cytokine profile and pathology in human leishmaniasis.

The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-gamma is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-gamma production and high IL-4 and IL-10 levels (Th2 cytokines) are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC). Moreover, IL-12 restores IFN-gamma production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-gamma production, since anti-IL-10 monoclonal antibody (mAb) restores in vitro IFN-gamma production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-gamma are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-gamma levels were observed in antigen-stimulated PBMC from 50% of subjects with less than 60 days of disease (24 +/- 26 pg/ml). This response was restored by IL-12 (308 +/- 342 pg/ml) and anti-IL-10 mAb (380 +/- 245 pg/ml) (P < 0.05). Later during the disease, high levels of IFN-gamma and TNF-alpha are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-alpha levels (366 +/- 224 pg/ml before treatment vs 142 +/- 107 pg/ml after treatment, P = 0.02). Although production of IFN-gamma and TNF-alpha might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis.

Animals↗
PubMed1998

Human_leishmaniasis/cytokines.bahia.br.

The cell-mediated immune response is critical in the resistance to and recovery from leishmaniasis. Cytokines are central elements in mounting an immune response and have received a great deal of attention in both human and experimental leishmaniasis. IFN-gamma is responsible for macrophage activation leading to leishmanicidal mechanisms. Understanding the balance of cytokines that lead to enhanced production of or synergize with IFN-gamma, and those cytokines that counterbalance its effects is fundamental for developing rational immunotherapeutic or immunoprophylactic approaches to leishmaniasis. Here we focus on the cytokine balance in human leishmaniasis, particularly IL-10 as an IFN-gamma opposing cytokine, and IL-12 as an IFN-gamma inducer. The effects of these cytokines were evaluated in terms of several parameters of the human immune response. IL-10 reduced lymphocyte proliferation, IFN-gamma production and cytotoxic activity of responsive human peripheral blood mononuclear cells. Neutralization of IL-10 led to partial restoration of lymphoproliferation, IFN-gamma production and cytotoxic activity in unresponsive visceral leishmaniasis patients. IL-12 also restored the responses of peripheral blood mononuclear cells from visceral leishmaniasis patients. The responses obtained with IL-12 are higher than those obtained with anti-IL-10, even when anti-IL-10 is combined with anti-IL-4.

Brazil↗
PubMed1998

Absence of linkage between MHC and a gene involved in susceptibility to human schistosomiasis.

Six hundred million people are at risk of infection by Schistosoma mansoni. MHC haplotypes have been reported to segregate with susceptibility to schistosomiasis in murine models. In humans, a major gene related to susceptibility/resistance to infection by S. mansoni (SM1) and displaying the mean fecal egg count as phenotype was detected by segregation analysis. This gene displayed a codominant mode of inheritance with an estimated frequency of 0.20-0.25 for the deleterious allele and accounted for more than 50% of the variance of infection levels. To determine if the SM1 gene segregates with the human MHC chromosomal region, we performed a linkage study by the lod score method. We typed for HLA-A, B, C, DR and DQ antigens in 11 informative families from an endemic area for schistosomiasis in Bahia, Brazil, by the microlymphocytotoxicity technique. HLA-DR typing by the polymerase chain reaction with sequence-specific primers (PCR-SSP) and HLA-DQ were confirmed by PCR-sequence-specific oligonucleotide probes (PCR-SSOP). The lod scores for the different theta values obtained clearly indicate that there is no physical linkage between HLA and SM1 genes. Thus, susceptibility or resistance to schistosomiasis, as defined by mean fecal egg count, is not primarily dependent on the host's HLA profile. However, if the HLA molecule plays an important role in specific immune responses to S. mansoni, this may involve the development of the different clinical aspects of the disease such as granuloma formation and development of hepatosplenomegaly.

Animals↗
PubMed1998

Regulation of T cell response to leishmania antigens by determinants of histocompatibility leukocyte class I and II molecules.

It has been shown that HLA class I molecules play a significant role in the regulation of the proliferation of T cells activated by mitogens and antigens. We evaluated the ability of mAb to a framework determinant of HLA class I molecules to regulate T cell proliferation and interferon gamma (IFN-gamma) production against leishmania, PPD, C. albicans and tetanus toxoid antigens in patients with tegumentary leishmaniasis and healthy subjects. The anti-major histocompatibility complex (MHC) mAb (W6/32) suppressed lymphocyte proliferation by 90% in cultures stimulated with alpha CD3, but the suppression was variable in cultures stimulated with leishmania antigen. This suppression ranged from 30-67% and was observed only in 5 of 11 patients. IFN-gamma production against leishmania antigen was also suppressed by anti-HLA class I mAb. In 3 patients IFN-gamma levels were suppressed by more than 60%, while in the other 2 cultures IFN-gamma levels were 36 and 10% lower than controls. The suppression by HLA class I mAb to the proliferative response in leishmaniasis patients and in healthy controls varied with the antigens and the patients or donors tested. To determine whether the suppression is directed at antigen presenting cells (APCs) or at the responding T cells, experiments with antigen-primed non-adherent cells, separately incubated with W6/32, were performed. Suppression of proliferation was only observed when the W6/32 mAb was added in the presence of T cells. These data provide evidence that a mAb directed at HLA class I framework determinants can suppress proliferation and cytokine secretion in response to several antigens.

Animals↗
PubMed1998

Anti-leishmanial IgE antibodies: a marker of active disease in visceral leishmaniasis.

Visceral leishmaniasis (VL) is characterized by a depression of the T helper cell type 1 immune response. Although mRNA expression for interleukin-4 (IL-4) is observed, evidence of the role of this cytokine in the pathogenesis of VL has been lacking. Since IL-4 is involved in IgE synthesis, we measured the total IgE and Leishmania antigen-specific IgE antibody levels in sera from patients with VL. Specific IgE antibodies detected by an ELISA technique after absorbing the sera with purified sheep IgG anti-human IgG were found in all 23 patients with VL and were not detected in subjects with subclinical Leishmania chagasi infection (n = 10), Chagas' disease (n = 10), atopic patients (n = 10), and healthy controls (n = 10). Levels of Leishmania-specific IgE (optical density values) before and after treatment were 0.100 +/- 0.03 (mean +/- SD) and 0.028 +/- 0.002, respectively (P < 0.05). These results indicate that a specific IgE response is useful in the diagnosis of active disease and to evaluate response to treatment.

Acute Disease↗
PubMed1998

Clinical observations of unresponsive mucosal leishmaniasis.

We report the long-term clinical follow-up of two patients with unresponsive mucosal leishmaniasis due to Leishmania (Viannia) braziliensis from the Três Braços area in Bahia State, Brazil. Both were agricultural male workers with extensive upper respiratory mucosal involvement that was not cured with conventional and experimental therapy.

Adult↗