International immunopharmacology
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Int. Immunopharmacol. · Oct 2007
Virulizin, a novel immunotherapy agent, stimulates TNFalpha expression in monocytes/macrophages in vitro and in vivo.
Virulizin, a novel biological response modifier, has demonstrated broad antitumor efficacy in a variety of human tumor xenograft models including melanoma, pancreatic cancer, breast cancer, ovarian cancer and prostate cancer. Previous studies have demonstrated a significant role of macrophages and NK cells in the antitumor mechanism of Virulizin. Increased activity and expansion of macrophages and NK cells has been observed in mice treated with Virulizin. ⋯ U937 cells treated with Virulizin showed a significantly enhanced cytotoxicity that was eliminated upon neutralization of TNFalpha. Virulizin also induced the phosphorylation of IkappaB, suggesting that induction of TNFalpha expression by Virulizin is mediated by activation of NFkappaB. The results indicate that Virulizin-induced TNFalpha expression contributes to modulation of immune responses and antitumor activities.
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Int. Immunopharmacol. · Aug 2007
Bee venom and melittin reduce proinflammatory mediators in lipopolysaccharide-stimulated BV2 microglia.
Bee venom (BV), well known as a traditional Oriental medicine, has been shown to exhibit anti-arthritic and anti-carcinogenic effects. However, the molecular mechanisms responsible for the anti-inflammatory activity of BV have not been elucidated in microglia. In the present study, we investigated the anti-inflammatory effect of BV and its major component, melittin (MEL), on lipopolysaccharide (LPS)-stimulated BV2 microglia. ⋯ Our data also indicate that BV and MEL exert anti-inflammatory effects by suppressing the transcription of cyclooxygenase (COX)-2 genes and proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha. BV and MEL also attenuated the production of prostaglandin E(2) (PGE(2)). These results demonstrate that BV and MEL possess a potent suppressive effect on proinflammatory responses of BV2 microglia and suggest that these compounds may offer substantial therapeutic potential for treatment of neurodegenerative diseases that are accompanied by microglial activation.
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Int. Immunopharmacol. · Aug 2007
Effects of ketamine on levels of cytokines, NF-kappaB and TLRs in rat intestine during CLP-induced sepsis.
This study was designed to investigate the effects of ketamine on levels of inflammatory cytokines, nuclear factor-kappa B (NF-kappaB) and Toll-like receptors (TLRs) in rat intestine during polymicrobial sepsis, induced by cecal ligation and puncture (CLP). After the induction of sepsis or sham-operation, the rats were treated with ketamine (2.5, 5 or 10 mg/kg) or saline (10 ml/kg). At 2, 4 or 6 h post-operation, the intestinal concentrations of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, were determined by enzyme-linked immunosorbent assay (ELISA). ⋯ Ketamine 2.5, 5 and 10 mg/kg after CLP decreased intestinal TNF-alpha level and NF-kappaB activity, and inhibited TLR2 and TLR4 expressions as well. These results suggest that ketamine may have anti-inflammatory effects, such as suppressing the levels of inflammatory cytokines and attenuating NF-kappaB activity, during polymicrobial sepsis. And these anti-inflammatory effects possibly correlate with the inhibitory influence of ketamine on TLR2 and TLR4 expressions.
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Int. Immunopharmacol. · Dec 2006
Peripheral CD4+ CD25+ Treg cell expansion in lung transplant recipients is not affected by calcineurin inhibitors.
CD4+CD25+ regulatory T (Treg) cells have been shown to play a role in allograft tolerance and their peripheral counts vary according to the degree of graft acceptance in lung transplant recipients (LTR). Recent studies demonstrate that certain drugs might modulate generation, expansion and activity of Treg cells. Aim of this study was to evaluate the effect of therapeutic regimens used in our institution on peripheral CD4+CD25(high)CD69- Treg cell numbers in a group of 51 LTR with stable clinical conditions. ⋯ During these treatments a significant expansion of Treg cell counts was detectable during acute rejection (AR) episodes (86.03+/-26.6/mul during AR versus 36.34+/-7.6 before AR; p<0,05). Moreover, the development of BOS was associated to a significant decrease of Treg cell counts irrespective to the immunosuppressive regimen used. In conclusion, therapeutic regimens based on CNI seem to allow a certain degree of peripheral Treg cell expansion in stable LTR.
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Int. Immunopharmacol. · Dec 2006
Clinical TrialEarly steroid withdrawal protocol with basiliximab, cyclosporine and mycophenolate mofetil in renal-transplant recipients.
Adverse effects of steroids have led to efforts to minimize their use in recipients of organ transplants. This study evaluated an early steroid withdrawal protocol including basiliximab, cyclosporine (CsA) and mycophenolate mofetil (MMF) in renal-transplant recipients. ⋯ Although further follow-up is necessary to confirm our results, our protocol successfully permitted the early withdrawal of steroids in 62% of renal-transplant recipients, with no resumption of steroid treatment during 3 years of follow-up.