Inflammatory bowel disease arthritis

Infliximab Anti-TNFa Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis... 

Anticytokine antibodies Infliximab Chimeric (mouse/human) monoclonal antibody against TNEa. Effective in the treatment of severe forms of rheumatoid arthritis where it can halt disease progression, or inflammatory bowel disease (EBD). 

KC706 stabilizes the inactive conformation of the mitogen-activated protein kinase p38a, a protein kinase involved in inflammatory reactions and cardiovascular functions. KC706 therefore holds the potential to treat conditions such as rheumatoid arthritis, psoriasis, inflammatory bowel disease and cardiovascular disease. This compound is currently being tested in phase II clinical trials with patients suffering from rheumatoid arthritis. 

In addition to those described above, some of the newest compounds emerging in SERM development are ER 3-selective ligands and pathway-selective modulators that target the interaction of the ERs with the transcription factor NFkB. While such compounds are in the early stages of clinical evaluation, thus far they demonstrate great potential for use in the treatment of inflammatory disorders such as arthritis, inflammatory bowel disease, and like other SERMs, cancer [4]. 

The first mouse monoclonal antibody specific for human CD3 was produced in 1979 and named orthoclone OKT3. Aside from its use in the laboratory, OKT3 became the first anti-CD3 antibody to be utilized in transplantation medicine, but its wider application was hampered by its immunogenic and mitogenic properties (reviewed in [6]). Consequently, humanized and engineered anti-CD3 antibodies were developed to circumvent these limitations (Table 1). Since T cells and the TCR are involved in many immunological diseases, it is not surprising that the application of CD3 antibodies is not restricted to the field of transplantation. For example, CD3 antibodies are tested in clinical studies of diseases such as autoimmune diabetes (type 1 diabetes), immune-mediated inflammatory arthritis and inflammatory bowel disease [7]. 

Human tumor necrosis factor (TNF) (Fig. 1) is a hormone-like proinflammatory peptide belonging to the group of cytokines. It is mainly produced by cells of the immune system in response to infection, inflammation, or cell damage. Disregulated TNF is an important factor in many pathological situations, like sqDsis, rheumatoid arthritis, inflammatory bowel disease (Crohn s disease), and Cachexia. The cytotoxic activity of TNF is of interest in development of new antitumoral strategies. 

Pathway selective ER ligands have been reported that selectively inhibit nuclear factor kB (NF-kB) mediated gene expression [71], Since NF-kB is a pivotal regulator of pro-inflammatory gene expression, ligands that selectively inhibit the NF-kB pathway could be developed for the treatment of chronic inflammatory diseases such as arthritis, atherosclerosis, sepsis, and inflammatory bowel disease... 

Two more recent studies have also addressed SNP polymorphisms and potential links to clinically relevant conditions. " Given the role in inflammation and cytokine expression, one study examined the potential for linkage to autoimmune diseases including type 1 diabetes, rheumatoid arthritis, and inflammatory bowel disease in a population of more than 2000 patients. No significant association was found with any of the SNPs. In contrast, a strong association was found between a single polymorphism (G-105A alteration in the promoter) and women with preeclampsia. " Women who had preeclampsia were 1.34 times more likely to carry this mutant allele. The role that this mutant plays in the condition is unknown. 

Sulfasalazine anti-inflammatory (arthritis, inflammatory bowel disease) [18,441-445]... 

Whereas initially the focus on antibody-based therapies was on cancer, anti-TNFa antibodies in particular have recently proven powerful in the therapy of chronic inflammatory diseases such as inflammatory bowel disease and rhemnatoid arthritis [71], These antibodies complex serum TNFa, the clinical benefit to RA patients most likely being the reduction of pro-inflammatory IL-6 and acute phase protein levels [9], Although they are directed against soluble proteins and as such will not serve as a drug carrier, they do show that targeted, i.e. selective, interference with a specific molecule or process can have a powerful effect without significant concomitant toxicity. 

Advancement in autoimmune and inflammatory disease treatment and diagnosis represents a critical worldwide need ranking in importance only behind management of cardiovascular disease and cancer to the medical practitioner. The list of related diseases is long major classes include rheumatoid arthritis, asthma, diabetes type 1, multiple sclerosis, and inflammatory bowel disease. 

Indications for glucocorticosteroids include adrenal insufficiency and inflammatory, non-infectious processes of all sorts such as various types of arthritis, auto-immune diseases, asthma, inflammatory bowel diseases, especially Crohn s disease but also ulcerative colitis and further many skin diseases and some diseases of the eye. Their antimitotic activity is used in various anti-cancer chemotherapeutic regimens. They still have an important place... 

The autoimmune rheumatic diseases consists of Rheumatoid Arthritis (RA), Spondylarthritis (SpA), Systemic Lupus Erythematosus (SLE), Polymyositis, Dermatomyositis, Polymyalgia Rheumatica, Acute Temporal Arteritis, Giant Cell Arteritis, Behcet s Disease, Sjorgren s Syndrome, Felty s Syndrome and Mixed Connective Tissue Disease (MCTD). Spondylarthritis (SpA) can be subdivided in Reactive Arthritis (ReA), Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), Arthritis associated with the inflammatory bowel diseases are Crohn s disease and Ulcerative Colitis (IBD), Undifferentiated SpA (UspA) and Sacro-ilitis, Juvenile SpA and Acute Anterior Uveitis (AAU). 

Arthritis of IBD comprises rheumatic syndromes associated with IBD. Inflammatory bowel disease consists of Crohn s disease and Ulcerative Colitis. Gut inflammation is common in patients with SpA. Around 25% of patients with chronic SpA have early features of Crohn s disease. 

Sulfasalazine (Azulfldine) was first introduced in 1940 as a treatment for rheumatoid arthritis. It was found that a number of patients with coexistent inflammatory bowel disease showed improvement of their GI symptoms, and the drug has subsequently been used for the treatment of patients with inflammatory bowel disease. 

It is a cyclic polypeptide with 11 amino acids. It selectively inhibits T-lymphocytes proliferation, IL-2 and other cytokine production. It is the most effective drug for prevention and treatment of graft rejection reaction. It is used in cardiac, hepatic, renal, bone marrow transplantation and as second line drug in rheumatoid arthritis, inflammatory bowel disease, dermato-myositis, bronchial asthma and certain other autoimmune diseases. 

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