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1. Introduction
2. Overview of presentation
3. Early experiments
4. Human cytokines in 1980s
5. Properties of cytokines
6. TNFalpha at a protein and a genomic level
7. TNFalpha and anti-TNFalpha antibodies
8. The location of the TNFalpha gene
9. TNF and lymphotoxin bind to shared receptors
10. Rheumatoid arthritis: burden of disease
11. RA - structural and molecular deformities
12. Pathology of RA
13. Key members of the KIR team
14. IL-1 and TNFalpha in RA
15. RA synovium's IL-1alpha synthesis
16. Importance of TNF in cytokine regulation in vitro
17. TNF and receptors in RA tissues
18. Anti TNF treatment in an animal model of RA
19. Cytokine cascade in RA
20. A molecular hypothesis
21. First anti-TNF (cA2/infliximab) in RA clinical trials
22. Infliximab's mechanism of action
23. Anti-TNF works and tolerated well (1992)
24. Initial RCT of anti-TNF therapy (infliximab) in RA
25. How does anti-TNF work?
26. Reduction of acute phase response by infliximab
27. Anti-TNF regulates IL-6 in RA in vivo
28. Anti-TNF therapy reduces cellularity
29. Reduction in synovial inflammatory cell infiltrate
30. Why is cellularity reduced?
31. Adhesion molecules on infliximab therapy
32. Serum E-selectin levels are reduced after anti-TNF
33. Infliximab effect on specific chemokines
34. Synovial biopsies before and after anti-TNF therapy
35. Anti-TNF and angiogenesis
36. Anti-TNF reduces retention/recruitment of WBC
37. Anti-TNF reduces vascularity
38. Proposed mechanisms of action
39. Infliximab regulates altered T and B cell immunity
40. Summary of biological effects of infliximab
41. Anti-TNF biologicals in the clinic
42. Efficacy in randomised clinical trials
43. Anti-TNF therapy in other diseases
44. Adverse events and safety issues
45. Limitations of anti-TNF therapy
46. After TNF: what are we looking for?

Topics Covered

• What are cytokines?
• Early experiments
• Human cytokines in the 1980s
• Identification of TNFalpha at protein and genomic level
• TNFalpha and anti-TNFalpha antibodies
• Rheumatoid arthritis (RA): burden of disease
• Pathology of RA
• IL-1 and TNFalpha
• Cytokine cascade in RA
• A molecular hypothesis
• First anti-TNF (cA2/infliximab) in clinical trials in RA
• How does anti-TNF work?
• Why is cellularity reduced?
• Anti-TNF therapy inhibits cartilage and especially bone destruction
• Infliximab regulates altered T and B cell immunity
• Biological effects of Infliximab
• Anti-TNF biologicals in the lab
• Efficacy in randomized clinical trials
• Effective anti-TNF therapy demonstrates shared TNF-pathways in other diseases
• Adverse events and safety issues
• Limitations of anti-TNF therapy
• After TNF: what are we looking for?

Links

Series:

• Innate Immunity

Categories:

• Clinical Practice
• Immunology
• Pharmaceutical Sciences

Therapeutic Areas:

• Immunology & Inflammation

Talk Citation

Maini, R. (2009, May 31). From bench to bedside: evolution of anti-TNFalpha therapy in rheumatoid arthritis [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved March 25, 2023, from https://hstalks.com/bs/1314/.
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Publication History

• Published on May 31, 2009

Financial Disclosures

• Prof. Sir Ravinder Maini has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.