RESUMO
BACKGROUND: Fibromyalgia (FM) is characterized by chronic, widespread muscular pain and tenderness and is generally associated with other somatic and psychological symptoms. Further, circulatory levels of proinflammatory cytokines (IL-1beta, TNF-alpha, and IL-6) may be altered in FM patients, possibly in association with their symptoms. Recently, rises in BMI have been suggested to contribute to increased circulating levels of proinflammatory cytokines in FM patients. Our aim was to measure the circulatory levels of proinflammatory cytokines to determine the influence of BMI on these levels in FM patients and healthy volunteers (HVs). In Spanish FM patients (n = 64) and HVs (n = 25), we measured BMI and serum concentrations of proinflammatory cytokines by capture ELISA. FINDINGS: There were significant differences in BMI levels between FM patients (26.40 +/- 4.46) and HVs (23.64 +/- 3.45) and significant increase in IL-6 in FM patients (16.28 +/- 8.13 vs 0.92 +/- 0.32 pg/ml) (P < 0.001). IL-1beta and TNF-alpha decreased in FM patients compared with HVs. By ANCOVA, there was no significant association between BMI and TNF-alpha (F = 0.098, p = 0.75) or IL-6 (F = 0.221, p = 0.63) levels in FM patients. CONCLUSIONS: Our analysis in FM patients of BMI as a covariate of proinflammatory cytokines levels showed that serum TNF-alpha and IL-6 levels are independent of BMI. Further studies are necessary to dissect these findings and their implication in future therapeutic approaches for FM patients.
RESUMO
OBJECTIVE: To classify Mycobacterium leprae isolates from multiple areas in Mexico based on variable number of tandem repeats of 6 base within the rpoT gene and three single nucleotide polymorphism (SNP), and to analyse their geographic distribution in the context of the origin of leprosy in Mexico. RESULTS: Analysis for rpoT genotyping of 64 samples collected in the west and southwestern areas revealed that 46 isolates were of the 4 copy type and 18 isolates were of the 3 copy type. All samples from the eastern coastal area (n = 24) and from the Yucatan peninsula (n = 12) were of the 3 copy type. Six isolates from the west and southwestern area were SNP-type 1, 13 isolates were SNP-type 2 and 45 isolates were SNP-type 3. Nineteen of 24 isolates from the eastern coastal area were SNP-type 3 and one was SNP-type 4. Seven isolates from the Yucatan peninsula were SNP-type 3 and one was SNP-type 4. CONCLUSION: The difference of the proportion of each genotype between the western areas and the eastern areas indicated the expansion of leprosy through different paths in Mexico.
Assuntos
Hanseníase/microbiologia , Mycobacterium leprae/genética , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , DNA Bacteriano/química , DNA Bacteriano/genética , Variação Genética , Hanseníase/epidemiologia , Repetições Minissatélites , Polimorfismo de Nucleotídeo Único , Fator sigma/química , Fator sigma/genéticaRESUMO
DDT is still widely used in several parts of the world to control malaria, typhoid and dengue vectors, even though its use was banned in many countries based on toxicity data in wild life species. DDT has been shown to have immunotoxic effects in mice and to increase susceptibility to intracellular pathogens such as Mycobacterium leprae. However, little is known about the mechanisms underlying this effect. Activated macrophages play an important defensive role against intracellular pathogens, therefore our objective was to evaluate the effect of in vitro exposure to technical grade DDT (a mixture of three forms: 1,1,1-thricloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) (85%), o,p'-DDT (15%) and o,o'-DDT (trace amounts)), p,p'-DDT, 1,1-dicloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane on the functional activation of J774A.1 macrophages and their capability to limit growth of intracellular pathogens, using Mycobacterium microti as a model. We evaluated cytotoxicity and the effect on cell proliferation of 2.5, 5.0 and 10 microg/ml of DDT compounds. Functional macrophage activity (NO(*) and O(2)(-) production, and mRNA expression of TNF-alpha, IL-1beta and iNO synthase) and the ability of treated cells to limit infection by M. microti in IFN-gamma-activated macrophages were evaluated in cells exposed to 2.5 microg/ml of DDT compounds. Doses of 5 and 10 microg/ml induced direct cytotoxic effects precluding meaningful analysis of the above parameters, whereas 2.5 microg/ml of all DDT compounds inhibited macrophage activity and reduced their ability to limit the intracellular growth of M. microti without inducing cytotoxicity. Technical grade DDT and p,p'-DDE were the more potent compounds. Therefore, exposure to DDT compounds could represent an important risk for infection development by those intracellular pathogens against which NO(*) and/or O(2)(-) production represent the main immune protective mechanism.
Assuntos
DDT/toxicidade , Ativação de Macrófagos/efeitos dos fármacos , Infecções por Mycobacterium/imunologia , Animais , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Diclorodifenil Dicloroetileno/toxicidade , Interleucina-1/biossíntese , Isomerismo , Camundongos , Óxido Nítrico/toxicidade , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase Tipo II , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/biossínteseRESUMO
La lepra es una enfermedad multifactorial en la que la función que desempeña la respuesta inmunitaria es preponderante; sin embargo, la inmunología aún no ofrece explicación para la lepra TT, en la que la respuesta inmunitaria celular parece estar intacta. Existen investigaciones que indican que si bien la información genética del huésped no es determinante para el desarrollo de la enfermedad, sí lo es para el tipo de enfermedad que desarrollará el individuo
Assuntos
Humanos , Hanseníase/imunologia , Formação de Anticorpos , Imunidade Celular , Antígeno de Mitsuda/administração & dosagem , Mycobacterium leprae/imunologiaRESUMO
Las manifestaciones clínicas de la lepra van desde una pequeña mancha hipocrómica hasta los tipos deformantes. Se considera que la adquisición de la infección es multifactorial involucrando no sólo la presencia del bacilo sino también las características genéticas e inmunitarias del huésped. La lepra constituye un modelo único para estudiar los mecanismos inmunitarios en el hombre