International immunopharmacology
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Int. Immunopharmacol. · Dec 2011
Assessment of plasmatic immunoglobulin G, A and M levels in septic shock patients.
Polyvalent immunoglobulin (Ig) therapy has been tested as adjunctive treatment in sepsis and septic shock, but its efficacy is still a matter of debate. This has been explained because clinical trials were mostly performed on small numbers of patients. Moreover, the endogenous level of circulating Ig in patients was never taken into account. ⋯ However, at D1-2 and D3-4, decreased circulating Ig level was significantly correlated with reduced plasmatic protein concentrations. Overall, our results suggest that an apparent hypogammaglobulinemia is present at D1-2 and D3-4 in septic shock patients, which seems to be related with reduced circulating protein concentration after septic shock. These results need to be confirmed in a larger cohort of patients.
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Int. Immunopharmacol. · Dec 2011
Experimental examination of anti-inflammatory effects of a 5-HT3 receptor antagonist, tropisetron, and concomitant effects on autonomic nervous function in a rat sepsis model.
A 5-HT(3) receptor antagonist, tropisetron, has been reported to exhibit an anti-inflammatory effect in chronic inflammatory diseases by antagonizing a particular subtype of serotonin receptors. We investigated whether overproduction of cytokines could be controlled by intervention with tropisetron in an animal model of sepsis and also examined the effects of tropisetron on autonomic nervous activity. ⋯ Intervention with a 5-HT(3) receptor antagonist can control excess cytokine production involved in the pathogenesis of severe sepsis/septic shock.
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Int. Immunopharmacol. · Nov 2011
Randomized Controlled TrialEffects of a cytokine inhibitor, JTE-607, on the response to endotoxin in healthy human volunteers.
It is generally regarded that the excessive production of cytokines plays an important role in the pathology of autoimmune diseases and septic shock. We have investigated the ability of JTE-607, a novel inhibitor of cytokine production, to modulate the inflammatory response to endotoxin in healthy human volunteers. Three cohorts of healthy male volunteers were recruited for a randomized, placebo-controlled, double-blind study. ⋯ The production of endotoxin-mediated interleukin (IL)-1 receptor antagonist was significantly inhibited at 0.3 mg/kg/h dose with mean % difference from placebo of -60% (P=0.0037). Endotoxin-induced C-reactive protein decreased with the increasing dose of JTE-607 with mean % difference from placebo of -32.1% (P=0.322), -82.9% (P=0.0001) and -90.3% (P<0.0001) at 0.03, 0.1 and 0.3 mg/kg/h dose, respectively. In conclusion, this study describes a cytokine modulator JTE-607, which inhibits production of IL-10, IL-1ra and C-reactive protein in a human model of endotoxemia.
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Int. Immunopharmacol. · Sep 2011
Ligustilide prevents LPS-induced iNOS expression in RAW 264.7 macrophages by preventing ROS production and down-regulating the MAPK, NF-κB and AP-1 signaling pathways.
Angelica sinensis (AS), an herb used in traditional Chinese medicine, is thought to have anti-inflammatory activities. Ligustilide is its most abundant ingredient. This study sought to determine ligustilide's effects on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. ⋯ Ligustilide also inhibited the phosphorylation of IκB kinase (IKK) and mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK). The intracellular reactive oxygen species (iROS) level was also significantly decreased. These results suggest that ligustilide exhibits anti-inflammatory activities by blocking the activation of MAPKs/IKK and the downstream transcription factors AP-1 and NF-κB, which may result from ligustilide's down-regulation of iROS production.
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Int. Immunopharmacol. · Sep 2011
Characterization, epitope identification and mechanisms of the anti-septic capacity of monoclonal antibodies against macrophage migration inhibitory factor.
Sepsis is characterized by uncontrolled inflammatory responses. Macrophage migration inhibitory factor (MIF) has been shown to play an important role in the progression of sepsis thus is a potential therapeutic target. The aim of this study is to produce IgG anti-MIF monoclonal antibodies (mAbs) with anti-septic abilities in vivo and to determine mechanisms of their function. ⋯ Three of the mAbs, F11 in particular, inhibited tautomerase activity in association with their protective effect on CLP mice. Thus, we have produced anti-MIF mAbs that protected mice from CLP-induced sepsis by recognizing the same epitope domains in MIF. These mAbs are promising candidates for further development of therapeutics against inflammatory diseases.