In this study, we addressed the role of tumor necrosis factor (TNF)-alpha and lymphotoxin (LT)-alpha in the development of colitis and defined the cellular sources (T cells versus non-T cells) of TNF (TNF-alpha and LT-alpha) relevant to disease development. After adoptive transfer of TNF(+/+) CD4(+)CD45RB(hi) splenocytes into TNF(+/+) recombination activating gene (RAG)2(-/-) mice, the recipien...

OBJECTIVE Migration of vascular smooth muscle cells (VSMCs) contributes to formation of vascular stenotic lesions such as atherosclerosis and restenosis after angioplasty. Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-alpha) is a potent migration factor for VSMCs. cAMP-response element-binding protein (CREB) is the stimulus-induced transcription factor and activates t...

Idiopathic pneumonia syndrome (IPS) is a significant cause of mortality after allogeneic bone marrow transplantation (allo-BMT), and tumor necrosis factor-alpha (TNF-alpha) is a significant effector molecule in this process. However, the relative contribution of donor-versus host-derived TNF-alpha to the development of IPS has not been elucidated. Using a lethally irradiated parent --> F1 mouse...

Langerhans cells act as antigen-presenting cells in immune reactions in the skin. What other roles they may play in inflammation is less well defined. We have tested whether these cells can produce TNF-alpha, an important mediator of inflammation. Resting Langerhans cells produce less than 0.1 U TNF-alpha/ml. Langerhans cells stimulated with phorbol myristate acetate (PMA) and lipopolysaccharid...

BACKGROUND AND PURPOSE Tumor necrosis factor-alpha (TNF-alpha) is detected in ischemic brain cells in experimental animal models and is believed to play an important role in apoptosis. However, the natural expression of TNF-alpha during human stroke is not known. METHODS We examined TNF-alpha immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL...

TNF-alpha expression is elevated in a variety of neuropathologies, including multiple sclerosis, cerebral malaria and HIV encephalitis. However, the consequences of such high cerebral TNF-alpha expression remain unresolved. Here, using MRI, we demonstrate that a focal intrastriatal injection of TNF-alpha causes a significant, acute reduction (15-30%) in cerebral blood volume (CBV), which is dep...

The effects of interleukin (IL)-8 on spontaneous IgE and IgG4 production in atopic patients were studied. IL-8 inhibited IgE and IgG4 production by purified surface (s) IgE+ and sIgG4+ B cells, respectively, while it had no effect on IgG1, IgG2, IgG3, IgM, IgA1, and IgA2 production by corresponding sIg+ B cells. The IL-8-induced inhibition was counteracted by IL-6 and tumor necrosis factor-alph...

Endotoxemia (LPS) can exacerbate ischemic tubular injury and acute renal failure (ARF). The present study tested the following hypothesis: that acute ischemic damage sensitizes the kidney to LPS-mediated TNF-alpha generation, a process that can worsen inflammation and cytotoxicity. CD-1 mice underwent 15 min of unilateral renal ischemia. LPS (10 mg/kg iv), or its vehicle, was injected either 45...

Although only 5-10% of patients with asthma are relatively unresponsive to treatment with inhaled corticosteroids, refractory asthma represents an important condition, as these patients suffer considerable morbidity and mortality and consume a disproportionately large amount of health resource. Treatment options are limited and there is a large unmet clinical need for additional therapies. Tumo...