Cytokines are molecules that act as mediators of immune response; cerebral spinal fluid (CSF) IL-6 is found in all meningeal inflammatory diseases, but IL-8 is associated with acute bacterial meningitis (ABM). A case control study was done to ascertain the discriminatory power of these cytokines in differentiating ABM from aseptic meningitis (AM); IL-6 and IL-8 CSF concentrations were tested through ELISA in samples collected from patients who underwent investigation for meningitis. Sixty patients, 18 with AM, nine with bacteriologic confirmed ABM and 33 controls, assisted in 2005 (MA and controls) and 2007 (ABM) were included. Differently from controls, IL-6 concentrations were increased both in MA and ABM patients (p < 0.05). CSF IL-8 levels were higher in ABM than in AM and controls (p < 0.05). Discriminatory power in ABM as assessed by the area under receiver operator (ROC) curve was 0.951 for IL-8, using a cut-off of 1.685 ng/dL (100% of sensitivity and 94% of specificity). The CSF concentration of both IL-6 and IL-8 are increased in the presence of meningeal inflammation, IL-8 could be an important tool to differentiate ABM from AM.

Corticosteroids are widely used to treat a diversity of pathological conditions including allergic, autoimmune and some infectious diseases. These drugs have complex mechanisms of action involving both genomic and non-genomic mechanisms and interfere with different signal transduction pathways in the cell. The use of corticosteroids to treat critically ill patients with acute respiratory distress syndrome and severe infections, such as sepsis and pneumonia, is still a matter of intense debate in the scientific and medical community with evidence both for and against its use in these patients. Here, we review the basic molecular mechanisms important for corticosteroid action as well as current evidence for their use, or not, in septic patients. We also present an analysis of the reasons why this is still such a controversial point in the literature.

Rheedia longifolia Planch et Triana belongs to the Clusiaceae family. This plant is widely distributed in Brazil, but its chemical and pharmacological properties have not yet been studied. We report here that leaves aqueous extract of R. longifolia (LAE) shows analgesic and anti-inflammatory effects. Oral or intraperitoneal administration of this extract dose-dependently inhibited the abdominal constrictions induced by acetic acid in mice. The analgesic effect and the duration of action were similar to those observed with sodium diclofenac, a classical non-steroidal analgesic. In addition to the effect seen in the abdominal constriction model, LAE was also able to inhibit the hyperalgesia induced by lipopolysaccharide from gram-negative bacteria (LPS) in rats. We also found that R. longifolia LAE inhibited an inflammatory reaction induced by LPS in the pleural cavity of mice. Acute toxicity was evaluated in mice treated with the extract for seven days with 50 mg/kg/day. Neither death, nor alterations in weight, blood leukocyte counts or hematocrit were noted. Our results suggest that aqueous extract from R. longifolia leaves has analgesic and anti-inflammatory activity with minimal toxicity and are therefore endowed with a potential for pharmacological control of pain and inflammation.

Platelet-activating factor (PAF) is one of the most potent lipid mediators involved in inflammatory events. The acetyl group at the sn-2 position of its glycerol backbone is essential for its biological activity. Deacetylation induces the formation of the inactive metabolite lyso-PAF. This deacetylation reaction is catalyzed by PAF-acetylhydrolase (PAF-AH), a calcium independent phospholipase A2 that also degrades a family of PAF-like oxidized phospholipids with short sn-2 residues. Biochemical and enzymological evaluations revealed that at least three types of PAF-AH exist in mammals, namely the intracellular types I and II and a plasma type. Many observations indicate that plasma PAF AH terminates signals by PAF and oxidized PAF-like lipids and thereby regulates inflammatory responses. In this review, we will focus on the potential of PAF-AH as a modulator of diseases of dysregulated inflammation.

Sepsis is a major challenge in medicine. It is a common and frequently fatal infectious condition. The incidence continues to increase, with unacceptably high mortality rates, despite the use of specific antibiotics, aggressive operative intervention, nutritional support, and anti-inflammatory therapies. Typically, septic patients exhibit a high degree of heterogeneity due to variables such as age, weight, gender, the presence of secondary disease, the state of the immune system, and the severity of the infection. We are at urgent need for biomarkers and reliable measurements that can be applied to risk stratification of septic patients and that would easily identify those patients at the highest risk of a poor outcome. Such markers would be of fundamental importance to decision making for early intervention therapy or for the design of septic clinical trials. In the present work, we will review current biomarkers for sepsis severity and especially the use of cytokines as biomarkers with important pathophysiological role.

Avaliamos em 38 pacientes com diabetes tipo 1 (DM1) e 24 não diabéticos, a suscetibilidade do LDL à oxidação in vitro. Foram avaliados glicemias de jejum e pós-prandial (GPP), hemoglobina glicosilada (HbA1c), perfil lipídico e análise espectrofotométrica da oxidação do LDL antes e 1, 3, 6 e 24 horas após adição de substância oxidante - sulfato de cobre (CuSO4). O coeficiente de oxidação do LDL foi semelhante nos dois grupos antes da adição do CuSO4. Entretanto, 3 horas após, o LDL se mostrou mais suscetível à oxidação in vitro nos pacientes com DM1. Houve correlação negativa com a GPP (r= -0,2511; p<0,05) e com a HbA1c (r= -0,2541; p<0,05). Concluímos que, em nossa amostra, o LDL dos pacientes com DM1 foi oxidado mais precocemente que o dos não diabéticos, e que o controle glicêmico apresentou importância neste evento.

In 38 patients with type 1 diabetes (DM 1) and 24 non-diabetics we investigated LDL susceptibility to in vitro oxidation. Fast and post-prandial glycaemia (PPG), glycated hemoglobin (HbA1c) and lipid profile were determined, together with an spectrophotometric analysis of LDL oxidation before and 1, 3, 6 and 24 hours after addition of the oxidant substance - copper sulphate (CuSO4). The LDL oxidation coefficient in the two groups presented similar basal values; however 3 hours after CuSO4, LDL was more oxidized in patients with DM1. There was a negative correlation with PPG (r= -0.2511; p<0.05) and HbA1c (r= -0.2541; p<0.05). We conclude that in our sample of DM patients LDL was oxidized earlier than in the non-diabetics and that the glycemic control is important in this event.

In the present work we review the existing evidence for a LPS-induced cytokine-mediated eosinophil accumulation in a model of acute inflammation. Intrathoracic administration of LPS into rodents (mice, rats or guinea pigs) induces a significant increase in the number of eosinophils recovered from the pleural fluid 24 hr later. This phenomenon is preceded by a neutrophil influx and accompanied by lymphocyte and monocyte accumulation. The eosinophil accumulation induced by LPS is not affected by inhibitors of cyclo or lipoxygenase nor by PAF antagonists but can be blocked by dexamethasone or the protein synthesis inhibitor cycloheximide. Transfer of cell-free pleural wash from LPS injected rats (LPS-PW) to naive recipient animals induces a selective eosinophil accumulation within 24 hr. The eosinophilotactic activity present on the LPS-PW has a molecular weight ranging between 10 and 50 kDa and its effect is abolished by trypsin digestion of the pleural wash indicating the proteic nature of this activity. The production of the eosinophilotactic activity depends on the interaction between macrophages and T-lymphocytes and its effect can not be blocked by anti-IL-5 monoclonal antibodies. Accumulated evidence suggest that the eosinophil accumulation induced by LPS is a consequence of a eosinophilotactic cytokine produced through macrophage and T-cell interactions in the site of a LPS-induced inflammatory reaction.