Anti-TNF-a antibody

TNF-a, therefore, promotes various aspects of immunity and inflammation. Blockage of its activity, e.g. by administration of anti-TNF-a antibodies, has been shown to compromise the body s ability to contain and destroy pathogens. 

The major types of drug therapy used in IBD include aminosalicylates, glucocorticoids, immunosuppressive agents (azathioprine, mercaptopu-rine, cyclosporine, and methotrexate), antimicrobials (metronidazole and ciprofloxacin), and agents to inhibit tumor necrosis factor-a (TNF-a) (anti-TNF-a antibodies). 

TNF-a is a cytokine produced by T cells and mast cells. TNF-a is involved in the gut inflammatory process in Crohn disease, where treatment with soluble TNF-a receptor and anti-TNF-a antibodies and soluble TNF-a receptor has the highest... 

As is implied by its name, the first TNF-a-dependent mechanism described was the induction of tumor necrosis in vivo through its role in tumor vasculature. However the mechanisms of the in vitro toxicity of TNF-a to tumor cells imply apoptosis rather than necrosis [97], Tumor necrosis in SCID (severe combined immuno-deficiency) mice treated with LPS does not lead to the rejection of tumors [98], Furthermore, necrosis and tumor regression must be dissociated since anti-IFN-y antibodies inhibit LPS-induced regression of Meth A sarcoma in mice, but not the necrotic hemorrhage attributed to TNF-a. It is now accepted that the antitumoral effect of TNF-a is indirect and dependent on acquired immune response. Matsumoto et al. [99] reported that, while TNF-a itself has no effect on hepatoma KDH-8 tumor cells in vitro, the antitumoral effect of the lipid A ONO-4007 against KDH-8 tumors in vivo is inhibited by anti-TNF-a antibodies in WKAH rat, showing an indirect effect of TNF-a. 

Acute inhibition of IL-lp by means of the IL-1 receptor antagonist (which is also an endogenous ligand of the IL-1 receptors), the soluble IL-1 receptor, or substances that inhibit IL-1 production is followed by decreases in spontaneous sleep (reviewed in Refs. 40,46). TNF-a can also be inhibited by administering anti-TNF-a antibodies or soluble TNFRs, and these substances decrease spontaneous sleep (reviewed in Refs. 40,46). Inhibition of either IL-lp or TNF-a also attenuates sleep rebound after sleep deprivation (40,46). Further, suppression of TNF also blocks enhancements in NREM sleep in response to a mild increase in ambient temperature (67). NREM sleep is permanently reduced in mutant mice lacking type 1 IL-1 receptors, but interestingly, the decreases in NREM sleep occur during the active period of the day (68). Decreases in NREM sleep were found in mice with deficient 55-kD TNF receptor in one study (47) but sleep was normal in mice with the same defect in another experiment (69). 

The pioneering work on monoclonal antibodies against TNF-a originate from Junming Le and Jan VUcek at the New York University School of Medicine. Infliximab (Retnicade ) is a chimeric, monoclonal anti-TNF-a-antibody (human/ mouse), which is approved for the treatment of rheumatoid arthritis, Crohn s disease (a chronic inflammatory disease of the intestine) and psoriasis. [210]... 

Extracellular reduced glutathione could completely attenuate the cristobalite (particle diameter 1.2 on)-induced expression of monocyte chemo-tactic protein-1 and macrophage inflammatory protein-2 mRNAs by a murine alveolar type II line, whereas TNF-a mRNA levels were unaltered (Barrett et al. 1999). Using the oxidant sensitive dye, 6-carboxyl-27 -dichlorodihydrofluorescein diacetate di(acetoxymethyl ester) treatment of this cell line with cristobalite (18 ftg/cnf = 100 pg/ial) and TNF-a (1 ng/ml) resulted in the production of reactive oxygen species, which could be inhibited with extracellular GSH treatment. In the case of cristo-balite-induced reactive oxygen species, inhibition was also achieved with an anti-TNF-a antibody. 

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