Inhibitory Effect of LPS-Induced Tumor Necrosis Factor in Calves Treated with Chlorpromazine or Pentoxifylline.

Abstract

ABSTRACT. The inhibitory effect of chlorpromazine (CPZ), pentoxifylline (PTX) and dexamethasone (DEX) was investigated in a model of endotoxin shock in Holstein calves following an intravenous administration of Esherichia coli endotoxin (LPS). Initial correlations with its effects on the levels of tumor necrosis factor (TNF), a pivotal mediator of endotoxin shock, and clinical signs were obtained. The pretreatment of CPZ or DEX significantly decreased the serum levels of TNF, and reduced endotoxic shock. But the pretreatment of PTX hardly reduced the increase of serum TNF levels and endotoxin shock. The levels of serum endotoxin were not significantly different a minute of postinjection of LPS in calves. The results of this study indicate that pretreatment of CPZ or DEX inhibit various biological effects on endotoxin in calves. -KEY WORDS: calf, LPS, TNF.

Effects of Chlorpromazine, Pentoxifylline and Dexamethasone on mRNA Expression of Lipopolysaccharide-Induced Inflammatory Cytokines in Bovine Peripheral Blood Mononuclear Cells.

“…PTX inhibited the mRNA expression of inflammatory cytokines in humans and mice [5,13], suggesting that PTX might have different pharmacologic effects in cattle. Previous studies reported that PTX did not inhibit the production of cytokines in cattle [8].…”

“…Inhibition of cytokine-gene expression was useful in the therapy of various gram-negative bacterial infections such as pneumonia and enteritis [9,14]. We have previously demonstrated that chlorpromazine (CPZ) and dexamethasone (DEX) reduced the increased TNF levels following Escherichia coli endotoxin challenge in calves, and pentoxifylline (PTX) did not reduce the increased TNF levels [8]. The purpose of the present study was to investigate the effects of CPZ, DEX, and PTX on the expression of proinflammatory cytokines in bovine peripheral blood mononuclear cells (PBMCs).…”

Effect of pentoxifylline on lung inflammation and gas exchange in a sepsis-induced acute lung injury model

“…Thus, the development of a sepsis model with welldefined respiratory dysfunction is important both as a tool to understand the pathogenesis of the disorder and as a model to test potential interventions. Different experimental approaches have been used to study pulmonary dysfunction in sepsis, among them CLP (17) and injection of LPS (18). The CLP model has been used very often because it mimics human peritoneal sepsis (17).…”

Inflammatory Cytokines and Antigen-Responsive Mononuclear Cells in Peripheral Blood of Cattle Infected with Salmonella Takoradi.

“…The specificity of IL-1 was confirmed according to the inhibition or reduction of its activity by goat anti-human IL-1 antibody. For the IL-6 assay, serum samples were treated at 56°C for 30 min and then assayed for proliferative activity on IL-6-dependent MH60/BSF2 cells using rhIL-6 as a standard [17].…”

“…TNF-α, in particular, plays a critical role in the pathogenesis of septic shock syndrome induced by endotoxemia [2,18]. During the course of septicemia and experimental endotoxemia, initiation of the cytokine network by TNF-α is followed by activation of other mediator systems, which is thought to be a major mediator to the development of septic shock syndromes, i.e., systemic inflammatory response syndromes (SIRS) [2,[16][17][18]25]. The undetectable TNF-α in the affected cattle in the present study might be attributed to low concentration of serum endotoxin or tolerance condition against endotoxin [2,19,25].…”