RESUMO
The aim of this study was to determine if macrophage inflammatory protein (MIP) 1alpha, MIP-1beta, and RANTES (regulated upon activation normally T-cell expressed and secreted) serum concentrations are associated with clinical manifestations, disease activity, and damage accrual in patients with systemic lupus erythematosus (SLE). A cross-sectional study was performed in 62 SLE patients (per American College of Rheumatology criteria) participating in a longitudinal study and 20 healthy subjects. MIP-1alpha, MIP-1beta, and RANTES serum concentrations were determined by enzyme-linked immunosorbent assay. Demographic parameters, clinical manifestations, serologic features, pharmacologic treatments, disease activity, and damage accrual were determined at study visit. Disease activity was assessed with the Systemic Lupus Erythematosus Activity Measure (SLAM), and disease damage was assessed with Systemic Lupus International Collaborating Clinic Damage Index (SDI). The relation between the variables was studied with the Student t test and the Pearson r correlation test. SLE patients were more likely to have higher concentrations of MIP-1beta and RANTES than healthy individuals. In addition, they had a trend to have higher concentrations of MIP-1alpha. Patients with discoid lupus were more likely to have higher levels of MIP-1alpha. Elevation of MIP-1beta correlated with higher SDI score. No association was found between serum chemokines levels and disease activity. In conclusion, SLE patients have higher serum levels of MIP-1beta and RANTES than healthy individuals. MIP-1alpha is associated with discoid lupus, and MIP-1beta correlates with damage accrual in SLE. This study suggests that chemokines may have a role in the pathogenesis of SLE.
Assuntos
Quimiocina CCL5/sangue , Lúpus Eritematoso Sistêmico/sangue , Proteínas Inflamatórias de Macrófagos/sangue , Adulto , Biomarcadores/sangue , Quimiocina CCL3 , Quimiocina CCL4 , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
HIV patients are predisposed to the development of hypertriglyceridemia and hypercholesterolemia as a result of both viral infection and HIV infection therapy, especially the protease inhibitors. Chemokines and cytokines are present at sites of inflammation and can influence the nature of the inflammatory response in atherosclerosis. We investigated the correlation between biochemical variables and beta-chemokines (MIP-1alpha and RANTES) and the apolipoprotein E genotype in HIV-infected individuals. The apolipoproteins were measured by nephelometry. Triglycerides and total cholesterol were determined by standard enzymatic procedures. The beta-chemokines were detected by ELISA. The genetic category of CCR5 and apolipoprotein E were determined by PCR amplification and restriction enzymes. Immunological and virological profiles were assessed by TCD(4)+ and TCD(8)+ lymphocyte counts and viral load quantification. Positive correlations were found between apo E and CD(8)+ (p = 0.035), apo E and viral load (p = 0.018), MIP-1alpha and triglycerides (p = 0.039) and MIP-1a and VLDL (p = 0.040). Negative correlations were found between viral load and CD(4)+ (p = 0.05) and RANTES and CD(4)+ (p = 0.029). The beta-chemokine levels may influence lipid metabolism in HIV-infected individuals.
Assuntos
Apolipoproteínas E/sangue , Quimiocina CCL5/sangue , Infecções por HIV/sangue , Lipoproteínas/sangue , Proteínas Inflamatórias de Macrófagos/sangue , Adulto , Apolipoproteínas E/genética , Biomarcadores/sangue , Relação CD4-CD8 , Quimiocina CCL3 , Quimiocina CCL4 , Feminino , Genótipo , Humanos , Masculino , Receptores CCR5/sangue , Carga ViralRESUMO
Chemokines play an important role during granulomatous inflammation in murine models of Schistosoma mansoni infection. Here, the expression and possible roles of chemokines during human S. mansoni infection were examined. Compared with uninfected individuals, infected patients had elevated plasma concentrations of macrophage inflammatory protein (MIP)-1alpha, RANTES (regulated on activation, normally T cell-expressed and secreted), and eotaxin. Concentrations of macrophage-derived chemokine, eotaxin-2, monocyte chemotactic protein-1, growth-related oncogene, and interleukin-8 were similar between the 2 groups. When subjects were grouped according to disease severity, individuals with a plasma MIP-1alpha concentration >400 pM had a 10-times greater risk of having the more severe hepatosplenic form of disease. In the in vitro granuloma reaction, greater concentrations of MIP-1alpha were produced by cells of patients with hepatosplenic disease than cells of patients with intestinal disease. Pretreatment with a chemokine receptor antagonist attenuated the enhanced in vitro reaction seen with cells derived from patients with hepatosplenic disease. MIP-1alpha may not only mark a subset of patients with a greater risk of having more severe disease but also play a relevant pathophysiological role in human schistosomiasis.
Assuntos
Proteínas Inflamatórias de Macrófagos/sangue , Schistosoma mansoni/imunologia , Esquistossomose mansoni/fisiopatologia , Adulto , Animais , Quimiocina CCL11 , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocina CCL5/sangue , Quimiocinas CC/sangue , Doença Crônica , Feminino , Humanos , Proteínas Inflamatórias de Macrófagos/fisiologia , Masculino , Contagem de Ovos de Parasitas , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/imunologiaRESUMO
The 32-bp deletion in the HIV-1 co-receptor CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals for the deleted allele and partial protection against HIV-1 during disease progression in heterozygotes. Natural ligands for CCR5, MIP-1alpha, MIP-1beta and RANTES, have been shown to inhibit HIV replication in CD4+ T cells. In the present study, we examined the CCR5 genotype by PCR and the plasma levels of RANTES and MIP-1alpha by ELISA among blood donors (N = 26) and among HIV-1-infected individuals (N = 129). The control group consisted of healthy adult volunteers and HIV-1-infected subjects were an asymptomatic and heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. The frequency of the CCR5 mutant allele (Delta32ccr5) in this population was 0.032; however, no Delta32ccr5 homozygote was detected. These results could be related to the intense ethnic admixture of the Brazilian population. There was no correlation between circulating beta-chemokines (MIP-1alpha, RANTES) and viral load in HIV-infected individuals. RANTES concentrations in plasma samples from HIV+ patients carrying the homozygous CCR5 allele (CCR5/CCR5) (28.23 ng/ml) were higher than in the control samples (16.07 ng/ml; P<0.05); however, this HIV+ patient group (mean 26.23 pg/ml) had significantly lower concentrations of MIP-1alpha than those observed in control samples (mean 31.20 pg/ml; P<0.05). Both HIV-1-infected and uninfected individuals heterozygous for the Delta32ccr5 allele had significantly lower concentrations of circulating RANTES (mean 16.07 and 6.11 ng/ml, respectively) than CCR5/CCR5 individuals (mean 28.23 and 16.07 ng/ml, respectively; P<0.05). These findings suggest that the CCR5 allele and beta-chemokine production may affect the immunopathogenesis of HIV-1.