Inflammation in rheumatoid arthritis

Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001 344( 12) 907—916. Cronstein BN. Low-dose methotrexate A mainstay in the treatment of rheumatoid arthritis. Pharmcol Rev 2005 57(2) 163—172. 

Ellingsen T, Buus A, Stengaard-Pedersen K. Plasma monocyte chemoattractant protein 1 is a marker for joint inflammation in rheumatoid arthritis. J Rheumatol... 

Choy EH, Pnaayi GS. 2001. Cytokine pathways and joint inflammation in rheumatoid arthritis. NEJM. 344 907-916. 

In the study of SLE patients, we and other authors have found that there is a correlation between SLE disease activity index (SLEDAI) and the production of IL-16 (L7) and IL-18 (W19). It was suggested that IL-16 and IL-18 may be a useful indicator of disease activity of SLE. Plasma MCP-1 concentration has also been proposed as a marker for monitoring joint inflammation in rheumatoid arthritis (El). 

New England Journal of Medicine 338 446-452 Choy E H S, Panayi G S 2001 Cytokine pathways cind joint inflammation in rheumatoid arthritis. New England Journal of Medicine 344 907-916 Creamer P, Hochberg M C 1997 Osteoarthritis. Lancet 350 503-509... 

Mellow Drug of America tenamfetamine. meloxicam (ban. inn] (UH ac 62 Mobic and many other names) is a member of the oxicam series, a CYCLOOXYGENASE INHIBITOR With NSAID ANALGESIC. ANTIINFLAMMATORY and ANTIPYRETIC activity. It is used orally to treat pain and inflammation in rheumatoid arthritis, and for short-term exacerbation of osteoarthritis. 

Liang et al. [90, 91] investigated controlled release of methotrexate using a PLLA microsphere delivery system, which was prepared by a solvent evaporation method, in synovial joints for the treatment of inflammation in rheumatoid arthritis. Methotrexate solution or methotrexate loaded microspheres were injected into the joint of healthy rabbits. The microsphere system showed an initial rapid burst of the drug followed by a slow release phase. In comparison to the solution, the microsphere system retained methotrexate in the joint cavity for a longer time. 

Riegsecker, S., Wiczynski, D., Kaplan, M.J., and Ahmed, S. 2013. Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis , Sciences., 93. 307-312. 

Unfortunately steroids merely suppress the inflammation while the underlying cause of the disease remains. Another serious concern about steroids is that of toxicity. The abmpt withdrawal of glucocorticoid steroids results in acute adrenal insufficiency. Long term use may induce osteoporosis, peptidic ulcers, the retention of fluid, or an increased susceptibiUty to infections. Because of these problems, steroids are rarely the first line of treatment for any inflammatory condition, and their use in rheumatoid arthritis begins after more conservative therapies have failed. 

Munthe, E., Kass, E. and Jellum, E. (1982). Evidence for enhanced radical scavenging prior to drug response in rheumatoid arthritis. In Advances in Inflammation Research (ed. S. Gorini) pp. 2II-2I8. Raven Press, New York. 

Indomethacin is used in rheumatoid arthritis, nonspecific infectious polyarthritis, gouty arthritis, osteoarthritis, ankylosing spondylitis, arthrosis, back pain, neuralgia, myalgia, and other diseases accompanied by inflammation. Synonyms for indomethacin are, among others, metindol, indacide, and rumacide. 

Inflammation is characterized by the orderly occurrence of several processes initiation of the event by a foreign substance or physical injury, recruitment and chemoattraction of inflammatory cells, and activation of these cells to release inflammatory mediators capable of damaging or killing an invading microbe or tumor. In some instances, the inflammatory response is initiated by an otherwise harmless foreign material (e.g., pollen). Inflammation can also result from an autoimmune response to the host s own tissue, as occurs in rheumatoid arthritis. 

Anakinra is a nonglycosylated form of the human IL-1 receptor antagonist (IL-lra). It is produced in a recombinant Escherichia coli expression system and has an additional methionine residue at its amino terminus. In rheumatoid arthritis patients, the amount of naturally occurring IL-lra in the synovial fluid is not sufhcient to counteract the high levels of locally produced IL-1. Anakinra acts as a competitive antagonist of the type 1 IL-1 receptor and decreases the pain and inflammation produced by IL-1. It is administered as a daily subcutaneous injection. 

Mecfianism of Action A monoclonal antibody that binds specifically to tumor necrosis factor (TNF) alpha, blocking its interaction with cell surface TNF receptors, Tfier-apeutic Effect Reduces inflammation, tenderness, and swelling of joints slows or prevents progressive destruction of joints in rheumatoid arthritis. 

Special interest in the prostaglandins has focused on pain of inflammation and allergic responses. The medical significance is easy to see. Five million Americans have rheumatoid arthritis, an inflammatory disease. Bronchial asthma and other allergic diseases are equally important. Our most common medicine is aspirin, an anti-inflammatory drug. Both the inflammatory response and the immune response are normal parts of the defense mechanisms of the body, but both are potentially harmful, and it is their regulation that is probably faulty in rheumatoid arthritis and asthma. Overproduction of prostaglandins may be a cause of menstrual cramps.308... 

IL-18 augments T- and NK-cell maturation, cytotoxicity and cytokine production. It stimulates TH differentiation, promotes secretion of TNF-a, IFN-y and GM-CSF and enhances NK cell cytotoxicity by increasing FasL expression. IL-8-mediated neutrophil chemotaxis is promoted by IL-18 via its effects on TNF-a and IFN-y, which are stimulatory in action. It plays an important role in maintaining synovial inflammation and inducing joint destruction in rheumatoid arthritis. In synovium of patients with rheumatoid arthritis, enhanced levels of TNF-a and IL-1 are associated with augmented expression of IL-18. 

In addition to direct effects on genes regulating inflammation, glucocorticoids also inhibit the transcription factors that initiate synthesis of pro-inflammatory cytokines (e.g., interleukin-1, tumor necrosis factor), enzymes (e.g., COX-2, nitric oxide synthase), and receptor proteins (e.g., natural killer receptors).17,87,89 Glucocorticoids may also exert some of their effects via a membrane-bound receptor that regulates activity of macrophages, eosinophils, T lymphocytes, and several other types of cells involved in the inflammatory response.89 Consequently, glucocorticoids affect many aspects of inflammation, and their powerful anti-inflammatory effects in rheumatoid arthritis result from their ability to blunt various cellular and chemical components of the inflammatory response. 

Several agents are now available that inhibit the action of tumor necrosis factor-alpha (TNF-a). TNF-a is a small protein (cytokine) that is released from cells involved in the inflammatory response. TNF-a seems to be a key chemical mediator that promotes inflammation and joint erosion in rheumatoid arthritis.83 Drugs that inhibit this chemical will therefore help delay the progression of this disease by decreasing TNF-a s destructive effects.70... 

Mechanism of Action. As indicated, these agents bind selectively to TNF-a (see Fig. 16-2).7,70,91 This action prevents TNF-a from binding to surface receptors located on other inflammatory cells. TNF is therefore unable to activate other inflammatory cells that cause inflammation and joint destruction in rheumatoid arthritis.70... 

Anakinra (Kineret) blocks the effects of interleukin-1 on joint tissues. Like TNF-a, interleukin-1 is a cytokine that promotes inflammation and joint destruction in rheumatoid arthritis.23,36 By blocking interleukin-1 receptors on joint tissues, anakinra prevents the destructive events mediated by this cytokine. This drug appears to be moderately effective in limiting the progression of rheumatoid arthritis, and it is generally well tolerated.36 Hence, anakinra is another option that can be used alone or in combination with other DMARDs such as methotrexate.23... 

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