Ubiquitin immunoreactivity in cerebrospinal fluid after traumatic brain injury: clinical and experimental findings.

Objective: Recent data indicate that ubiquitin is increased in serum after trauma and might regulate immune functions. Its cellular source is unknown. Because there have been no previous studies after traumatic brain injury (TBI), we determined whether ubiquitin immunoreactivity is increased in cerebrospinal fluid (CSF) after TBI.

Cytosolic ubiquitin and ubiquitylation rates in human peripheral blood mononuclear cells during sepsis.

The ubiquitin system plays a crucial role in the immune system, and ubiquitylation is regarded as one of the most common posttranslational modifications of proteins. However, its regulation in human peripheral blood mononuclear cells during sepsis is unknown. Thus, we investigated cytosolic levels of free and conjugated ubiquitin and the total ubiquitylation rate in cell free extracts from healthy donors (n = 10) and patients (n = 10) with sepsis.

Alterations in leukocyte function following surgical trauma: differentiation of distinct reaction types and association with tumor necrosis factor gene polymorphisms.

Endotoxin-stimulated blood cytokine responses have been widely used to describe compromised host defense mechanisms after trauma. We investigated whether blood cytokine production after endotoxin stimulation is able to define distinct trauma-induced alteration patterns and whether alteration patterns are associated with tumor necrosis factor (TNF) gene polymorphisms. In 48 patients undergoing joint replacement, the levels of TNF alpha (TNF-alpha), interleukin 6 (IL-6), and IL-8 production in blood after endotoxin stimulation were measured preoperatively on the day of surgery and 24 h thereafter.

Extracellular ubiquitin inhibits the TNF-alpha response to endotoxin in peripheral blood mononuclear cells and regulates endotoxin hyporesponsiveness in critical illness.

Ubiquitin is suggested to play a key role in essential intracellular functions, such as heat shock response, protein breakdown, and regulation of immune responses. Ubiquitin has also been detected in the extracellular space, but the function and biologic significance is unclear. We describe a new function of extracellular ubiquitin and show that extracellular ubiquitin specifically inhibits ex vivo secretion of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha mRNA expression from peripheral blood mononuclear cells (PBMNCs) in response to endotoxin in a dose-dependent manner.

Effects of antimicrobial agents on spontaneous and endotoxin-induced cytokine release of human peripheral blood mononuclear cells.

Because the immunomodulatory effects of antibiotics could possibly influence the degree of the systemic and local response to infection, knowledge of their intrinsic influence on the host's inflammatory response appears to be essential. Therefore, this study investigated the effects of frequently used antimicrobial agents (beta-lactams, quinolones gentamicin, vancomycin and metronidazole) on the in-vitro tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production of isolated human peripheral blood mononuclear cells (PBMNC), cultured with or without endotoxin, in comparison with those effects obtained in a whole-blood assay system. In the presence of ciprofloxacin, ofloxacin, gentamicin, vancomycin, and metronidazole, a significant inhibition of the endotoxin-stimulated TNF-alpha production of human peripheral blood mononuclear cells (PBMNC) was found at therapeutic levels.