Interleukin-8 and nuclear factor kappa B are increased and positively correlated in myelodysplastic syndrome.

The pathogenesis of myelodysplastic syndromes (MDS) is complex and depends on the interaction between aberrant hematopoietic cells and their microenvironment, probably including aberrations in cytokines and their signaling pathways. To evaluate interleukin-8 (IL-8) plasma levels and nuclear factor kappa B (NF-kB) in patients with MDS and to test possible correlation between IL-8 and NF-Kb, a total of 45 individuals were analyzed: 25 consecutive adult de novo MDS patients and 20 sex and age-matched healthy elderly volunteers. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay. MDS patients showed higher level of IL-8 when compared to controls (p = 0.006). Patients aged 75 and above showed even higher levels (p = 0.035). NF-kB activity was significantly elevated in MDS patients when compared to controls (p < 0.0001) and higher in patients older than 75 years (p = 0.047). NF-kB activity was associated with higher serum ferritin (p = 0.042) and higher percentage of blasts (p = 0.028). A significant positive correlation between IL-8 and NF-kB was demonstrated (r = 0.480; p = 0.015). Many pathways involved in pathophysiology of MDS have been recently described, suggesting that an inflammatory process may act as a pathogenic driver. In this study, significantly elevated levels of IL-8 and NF-kB were demonstrated in MDS patients, with positive association of NF-kB with some markers of poor prognosis. A positive correlation between IL-8 and NF-kB suggests they cooperate as part of a complex networking of immune and inflammatory factors involved in MDS.

Calea uniflora Less. attenuates the inflammatory response to carrageenan-induced pleurisy in mice.

Calea uniflora Less. (family Asteraceae), also named "arnica" and "erva-de-lagarto", is a native plant to the South and Southeast of Brazil. This species was used to treat rheumatism, respiratory diseases, and digestive problems in Brazilian folk medicine. In vitro studies have shown the important biological effects of C. uniflora. However no studies have focused on the mechanism of action of anti-inflammatory activity of C. uniflora. The aim of this study was to evaluate the anti-inflammatory effects of the crude extract, its fractions, and isolated compounds obtained from of C. uniflora, using mouse model of carrageenan-induced inflammation. The following inflammatory parameters: leukocyte influx, degree of exudation, myeloperoxidase (MPO) and adenosine deaminase (ADA) activities, nitric oxide metabolites (NOx), proinflammatory cytokines and phosphorylation of the p65 subunit of NF-κB (p-p65 NF-κB), and p38 mitogen-activated protein kinase (p-p38 MAPK) levels were determined. The crude extract of C. uniflora, its fractions and its isolated compounds reduced the leukocyte influx, degree of exudation, MPO and ADA activities, NOx, TNF-α, IFN-γ, MCP-1 and IL-6 levels (p<0.05). The isolated compounds reduced p-p65 NF-κB and p-p38 MAPK levels (p<0.01). This study demonstrated that C. uniflora exhibits a significant anti-inflammatory activity via inhibition of the leukocyte influx and degree of exudation. These effects were associated with a decrease in the levels of several proinflammatory mediators. The mechanism of the anti-inflammatory action of C. uniflora may be, at least in part, via the inhibition of p65 NF-κB and p38 MAPK activation by the isolated compounds.

Intra-Articular Blockade of P2X7 Receptor Reduces the Articular Hyperalgesia and Inflammation in the Knee Joint Synovitis Especially in Female Rats.

Synovitis is a key factor in joint disease pathophysiology, which affects a greater proportion of women than men. P2X7 receptor activation contributes to arthritis, but whether it plays a role in articular inflammatory pain in a sex-dependent manner is unknown. We investigated whether the P2X7 receptor blockade in the knee joint of male and female rats reduces the articular hyperalgesia and inflammation induced by a carrageenan knee joint synovitis model. Articular hyperalgesia was quantified using the rat knee joint incapacitation test and the knee joint inflammation, characterized by the concentration of cytokines tumor necrosis factor-α, interleukin-1ß, interleukin-6, and cytokine-induced neutrophil chemoattractant-1, and by neutrophil migration, was quantified using enzyme-linked immunosorbent assay and by myeloperoxidase enzyme activity measurement, respectively. P2X7 receptor blockade by the articular coadministration of selective P2X7 receptor antagonist A740003 with carrageenan significantly reduced articular hyperalgesia, pro-inflammatory cytokine concentrations, and myeloperoxidase activity induced by carrageenan injection into the knee joint of male and estrus female rats. However, a lower dose of P2X7 receptor antagonist was sufficient to significantly induce the antihyperalgesic and anti-inflammatory effects in estrus female but not in male rats. These results suggest that P2X7 receptor activation by endogenous adenosine 5'-triphosphate is essential to articular hyperalgesia and inflammation development in the knee joint of male and female rats. However, female rats are more responsive than male rats to the antihyperalgesic and anti-inflammatory effects induced by P2X7 receptor blockade. PERSPECTIVE: P2X7 receptors could be promising therapeutic targets in the treatment of knee joint disease symptoms, especially in women, who are more affected than men by these conditions.