TNF-a blockers

Mohan, A.K. et al., Drug-induced systemic lupus erythematosus and TNF-alpha blockers, Lancet 360,646, 2002. 

Bezombes, C., Maestre, N., Laurent, G., Levade, T., Bettaieb, A., and Jaffrezou, J. P., 1998, Restoration of TNF-a-induced ceramide generation and apoptosis in resistant human leukemia KGla cells by the P-glycoprotein blocker PSC833. FASEB J. 12 101-109. 

Lee YH, Ji JD, Bae SC, Song GG (2010) Associations between tumor necrosis factor-alpha (TNF-alpha) -308 and -238 G/A polymorphisms and shared epitope status and responsiveness to TNF-alpha blockers in rheumatoid arthritis a metaanalysis update. J Rheumatol 37 740-746... 

Ca -free media (Moller etal. 2000). It was blocked by thapsigargin, indicating that thrombin caused a Ca release from internal stores. Preincubation with pertussis toxin did not alter the thrombin-induced [Ca Ji signal, whereas it was blocked by hirudin, a blocker of the proteolytic activity of thrombin. Incubation with thrombin led to the production of nitric oxide and the release of the cytokines TNF-a, IL-6, IL-12, the chemokine KC, and the soluble tumour necrosis factor-a receptor II and had a significant proliferative effect. 

No drug interaction studies have been conducted in humans. Animal studies indicate no change in the clearance or toxicity of either methotrexate or anakinra when the two agents are administered together. Concomitant administration of a TNF blocker appears to increase the risk of serious infection. The response to vaccines may be diminished in patients taking anakinra. 

The potential role of TNF-blocking therapy in the development of malignancies is not known. Rates in clinical trials of Remicade cannot be compared to rates in clinical trials of other TNF-blockers and may not predict rates observed in a broader patient population... 

People with moderate to severe active rheumatoid arthritis who have not been helped by TNF blockers might consider abatacept, which is administered IV monthly. Side effects may include headache, nausea, and mild infections, such as upper respiratory tract infections. Serious infections, such as pneumonia, can occur. There is some concern that blocking of the suppressive signal from B7 to CTLA-4 may have a negative effect on regulatory T cells and, thus, eventually, promote autoimmunity. 

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