Alice Santos-Silva

The inflammatory response in mild and in severe psoriasis

Background  Psoriasis is a chronic and recurrent inflammatory skin disease. The inflammatory response represents a fundamental ability of the organism to protect itself from infectious agents and from injury.

Dislipidemia and oxidative stress in mild and in severe psoriasis as a risk for cardiovascular disease

Psoriasis is a common chronic and recurrent inflammatory skin disorder that has been associated with oxidative stress, abnormal plasma lipid metabolism and with high frequency of cardiovascular events. This prevalence seems to be related to the severity of psoriasis, as it occurs more frequently in patients presenting large areas of the body affected with psoriasis lesions. The aim of our work was to evaluate the development of oxidative stress and of dislipidemia in psoriasis, and to look for a correlation between their levels and worsening of psoriasis. We evaluated lipid profile, total antioxidant capacity, antioxidant vitamins A and E, and lipoperoxidation products. The study was performed in controls and in patients presenting mild and severe psoriasis. Patients presented risk changes in lipid profile (a rise in cholesterol (P<0.01), triglycerides (P<0.001), low density lipoprotein cholesterol (P<0.01), very low density lipoprotein cholesterol (P<0.01), apolipoprotein B (P<0.001) and lipoprotein(a) (P<0.001); and a reduction in high density lipoprotein cholesterol (P<0.001)), a rise in lipoperoxidation products (P<0.001) and a reduction in total antioxidant capacity (P<0.001) and in antioxidant vitamins A (P<0.001) and E (P<0.05). Moreover, we found that the worsening of psoriasis was associated with the enhancement of oxidative stress and of the lipid risk changes. Our data suggest that psoriasis patients must be considered as a group at risk for cardiovascular disease and that this risk seems to be higher in severe psoriasis. In addition, a possible benefit of an enriched diet or of a supplement of vitamins A and E in psoriasis patients should be further studied.

Leukocyte activation, erythrocyte damage, lipid profile and oxidative stress imposed by high competition physical exercise in adolescents.

BACKGROUND The aim of this study was to evaluate and to compare the lipid profile and the levels of leukocyte activation, red blood cell (RBC) damage and of oxidative stress in two groups of adolescents, with similar body mass index: high competition swimmers and adolescents practising moderate regular physical exercise. METHODS As markers of leukocyte activation, we measured plasma lactoferrin, elastase and granulocyte-monocyte colony stimulating factor. We studied RBC membrane band 3 profile and membrane-bound hemoglobin, as markers of RBC damage and aging; total and differential leukocyte count and RBC count, hematocrit, hemoglobin concentration and hematimetric indexes were also measured. Lipid profile included the evaluation of triglycerides (TG), total cholesterol (Chol), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), apolipoproteins AI and B (Apo AI and B), and lipoprotein (a) (Lp(a)). To evaluate oxidative stress, lipoperoxidation products and total antioxidant capacity were measured. RESULTS We found that high competition adolescents presented increased plasma levels of leukocyte activation products, increased RBC damage suggesting aging and premature removal, and higher oxidative stress. Lipid profile showed some risk and some protective changes. CONCLUSIONS Our data suggest that high competition exercise, by imposing a higher and sustained oxidative and proteolytic stress, may contribute in the future to a higher risk of cardiovascular disease. We believe these findings warrant a reevaluation of current views in the intensity, duration and regularity of physical exercise, and that the evaluation of leukocyte activation products, RBC damage, oxidative stress and lipid profile may represent good markers to establish putative protective thresholds.

Interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor and tumour necrosis factor-α levels in patients with psoriasis before, during and after psoralen-ultraviolet A and narrowband ultraviolet B therapy.

Background  Several cross‐sectional studies have shown that different cytokines and growth factors are enhanced in psoriasis.

C-reactive protein and leucocyte activation in psoriasis vulgaris according to severity and therapy

Background  Psoriasis vulgaris is a chronic recurrent inflammatory skin disease and psoriatic lesions have shown leucocyte infiltration.

Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass index, severity and therapy

Background  Psoriasis vulgaris is associated with overweight/obesity and with increased C‐reactive protein (CRP), tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, leptin and resistin levels and decreased adiponectin levels.

The roles of cells and cytokines in the pathogenesis of psoriasis

Psoriasis is considered an immune chronic disease in which T cells are accepted as important. Nowadays, it is believed that psoriasis is most likely a T helper (Th)1/Th17 induced inflammatory disease. However, some other cells, such as endothelial cells, dendritic cells, monocytic cells, neutrophils, keratinocytes, and several cytokines, appear to have, at different stages of the disease, an important role in its pathogenesis. For instance, the response to psoriasis therapy is dependent not only on the inactivation of Th1 and Th17 immune responses but also on the inactivation of dendritic cell products. Moreover, interleukin (IL)‐23 deregulation appears to be an independent factor in the pathogenesis of psoriasis. Indeed, currently, the IL‐23/Th17 axis is believed to be crucial in psoriasis pathogenesis, and its inhibition appears to be important for therapeutic achievement. This review presents the roles and interactions of cells and cytokines that are related to psoriasis pathogenesis.

Inflammation, T-Cell Phenotype, and Inflammatory Cytokines in Chronic Kidney Disease Patients Under Hemodialysis and its Relationship to Resistance to Recombinant Human Erythropoietin Therapy

BackgroundResistance to recombinant human erythropoietin (rhEPO) occurs in some chronic kidney disease (CKD) patients, which may be due to enhanced systemic inflammatory response and to the erythropoiesis-suppressing effect of pro-inflammatory cytokines, some of which are produced by T cells.Aim of studyThe aim of this study was to investigate the relationship between resistance to rhEPO therapy in hemodialysis CKD patients and inflammatory markers [C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (sIL2R), and serum albumin levels], blood cell counts, T-cell phenotype, cytokine production by T cells, and serum cytokine levels.Materials and MethodsWe studied 50 hemodialysis CKD patients, 25 responders and 25 nonresponders to rhEPO, and compared them to each other and with 25 healthy controls. When compared to controls, CKD patients showed increased serum levels of CRP, IL-6, and sIL2R and a T-cell lymphopenia, due to decreased numbers of both CD4+ and CD8+ T cells. T cells from CKD patients had an immunophenotype compatible with chronic T-cell stimulation as shown by the increased percentage of CD28−, CD57+, HLA-DR+, CD28−HLA-DR+, and CD57+ HLA-DR+ T cells and produce higher levels of IL-2, INF-γ, and TNF-α after short-term in vitro stimulation, although Th1 cytokines were not detectable in serum. Statistically significant differences were found between responders and nonresponders to rhEPO therapy for total lymphocyte and CD4+ T-lymphocyte counts, albumin (lower in nonresponders) and CRP (higher in nonresponders) levels.ConclusionCKD patients under hemodialysis present with raised inflammatory markers and decrease of total lymphocyte and CD4+ T-lymphocyte counts when compared with controls. Some of those markers are even further enhanced in nonresponders to rhEPO therapy patients, but resistance to this therapy cannot be justified by a Th1 polarized T-cell response.

Neutrophil Activation and C‐Reactive Protein Concentration in Preeclampsia

Preeclamptic pregnancies seem to be associated with a higher extent of inflammation compared with normal ones. We intended to test this proposal and also to clarify the contribution of some variables in such inflammatory process. We measured total and differential leukocyte count, serum C‐reactive protein (CRP), and plasma levels of lactoferrin, elastase, and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Uric acid was also evaluated and used as an indicator of the severity of the disease. A cross‐sectional study was performed by evaluating healthy and preeclamptic women in the third trimester of gestation (n = 67 and n = 51, respectively) and 24 to 48 h postpartum (n = 32 and n = 26, respectively). When comparing the third trimester of normal and preeclamptic pregnancies, we found significantly higher levels of uric acid, CRP, and elastase, and a significantly higher elastase to neutrophil ratio in the pathologic group. However, for CRP, statistical significance was lost after adjustment for maternal weight. No significant differences were found in total leukocyte count, plasma levels of GM‐CSF, and lactoferrin between groups. In preeclampsia, a significant positive correlation was found between elastase and lactoferrin and these neutrophil activation products correlated positively with uric acid level. Considering the analysis of all variables in the postpartum period, only CRP and uric acid levels were significantly elevated in the pathologic group. However, CRP differences obtained in the puerperium seem to be influenced by the increased number of dystocic deliveries in the preeclamptic group. In conclusion, our data suggest that inflammation is further pronounced in preeclampsia and that the extent of neutrophil activation correlates with the severity of this syndrome.

Inflammatory Disturbances in Preeclampsia: Relationship between Maternal and Umbilical Cord Blood

Preeclampsia (PE) is one of the main causes of maternal and fetal mortality and morbidity. PE is associated with an inflammatory state and with oxidative stress, in maternal circulation. Our aim was to evaluate and compare the levels of oxidative stress and inflammatory markers in maternal and umbilical cord blood (UCB), in normal and PE pregnancies. We measured acute-phase proteins (CRP and α1-antitrypsin), proinflammatory cytokines (IL-6 and TNF-α), leukocyte activation (elastase, lactoferrin, sL-selectin, sVCAM, sPECAM), total antioxidant status (TAS), thiobarbituric acid reactive substances (TBARS), and uric acid levels. We studied 42 healthy pregnant women, 46 PE women, and their neonates. The concentrations of IL-6, TNF-α, α1-antitrypsin, CRP, sVCAM, uric acid, and TBARS were significantly higher, and sL-selectin was significantly lower in PE pregnant women as compared with normotensive pregnant women. In newborns uric acid, α1-antitrypsin, and CRP values were significantly higher in PE; leukocyte count, sL-selectin, lactoferrin, and the ratio elastase/α1-antitrypsin were significantly lower. Our data suggest that PE pregnancy is associated with an enhanced maternal inflammatory condition, which is reflected in fetal circulation. This enhanced inflammatory state seems to be related to endothelial dysfunction and increased cytokine synthesis, rather than with neutrophil activation.