PMID- 12236617
OWN - NLM
STAT- MEDLINE
DCOM- 20030319
LR  - 20151119
IS  - 0380-0903 (Print)
IS  - 0380-0903 (Linking)
VI  - 65
DP  - 2002 Sep
TI  - The mode of action of cytokine inhibitors.
PG  - 16-21
AB  - Tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 (IL-1) are important 
      mediators of inflammation and tissue damage in animal models of inflammatory 
      arthritis and in patients with active rheumatoid arthritis (RA). Several 
      inhibitors of these cytokines are now available for RA treatment, each having a 
      different mode of action. Etanercept is a recombinant fusion protein of the 
      soluble type II TNF receptor on a human IgG1 backbone, whereas infliximab is a 
      chimeric anti-TNF-alpha monoclonal antibody containing a murine TNF-alpha binding 
      region and human IgG1 backbone. Both agents potently and selectively bind 
      TNF-alpha in the cellular microenvironment, thereby preventing TNF-alpha from 
      interacting with membrane-bound TNF receptors on target cells. In comparison, 
      anakinra is a recombinant human IL-1 receptor antagonist (IL-1Ra) that binds 
      avidly to type 1 IL-1 receptors but does not stimulate any intracellular 
      responses. Studies of these agents in animal models of inflammatory arthritis 
      suggest that TNF-alpha plays a more important role in promoting inflammation, 
      whereas IL-1 is more important in causing cartilage and bone destruction. 
      However, these differential actions have not been borne out in clinical trials, 
      where TNF-alpha blockers and anakinra similarly reduce clinical signs and 
      symptoms of RA as well as slow radiographic evidence of disease progression.
FAU - Arend, William P
AU  - Arend WP
AD  - University of Colorado Health Sciences Center, Denver 80262, USA. 
      william.arend@uchsc.edu
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Canada
TA  - J Rheumatol Suppl
JT  - The Journal of rheumatology. Supplement
JID - 7806058
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cytokines)
RN  - 0 (IL1RN protein, human)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - B72HH48FLU (Infliximab)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*administration & dosage
MH  - Arthritis, Rheumatoid/diagnosis/*drug therapy/*physiopathology
MH  - Clinical Trials as Topic
MH  - Cytokines/*antagonists & inhibitors/metabolism
MH  - Disease Models, Animal
MH  - Etanercept
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunoglobulin G/*administration & dosage
MH  - Infliximab
MH  - Interleukin 1 Receptor Antagonist Protein
MH  - Interleukin-1/metabolism
MH  - Receptors, Tumor Necrosis Factor/*administration & dosage
MH  - Sensitivity and Specificity
MH  - Severity of Illness Index
MH  - Sialoglycoproteins/*administration & dosage
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/drug effects/metabolism
RF  - 43
EDAT- 2002/09/19 10:00
MHDA- 2003/03/20 04:00
CRDT- 2002/09/19 10:00
PHST- 2002/09/19 10:00 [pubmed]
PHST- 2003/03/20 04:00 [medline]
PHST- 2002/09/19 10:00 [entrez]
PST - ppublish
SO  - J Rheumatol Suppl. 2002 Sep;65:16-21.