Immune/inflammatory disorders

The neuropeptide Y (NPY) belongs to a family of peptides that includes peptide YY and pancreatic polypeptide, and it is associated with several diseases such as asthma, immune system disorders, inflammatory diseases, anxiety, depression and diabetes mellitus. NPY is found in the central and peripheral nervous system, and its biological functions are mediated by interactions with five receptor sub-types, i.e. Yl, Y2, Y4, Y5 and Y6. Several studies indicate that the feeding behavior is influenced by interactions between NPY and Yl and Y5. Deswal and Roy used Cerius descriptors and genetic function approximation QSAR to investigate the structural determinants for the inhibition potency of 24 compounds with the general structure 4 for the NPY Y5 receptor [31]. The best QSAR (H = 0.720,... 

Approximately 30% to 40% of currently licensed drugs are targeted at GPCRs and thus represent a highly significant source of income for many pharmaceutical companies (80). In the specific context of chemokine receptors, it is clear that they are involved in a number of prominent pathologies and thus represent an important therapeutic target (81). For example, chemokines and their receptors lie at the center of all immune and inflammatory disorders and are responsible for the aberrant accumulation of leukocytes at inflamed sites in autoimmune conditions. In addition, over the past 12 years, it has become clear... 

CMC), a primary immune deficiency presenting as an inability to clear yeasts, mostly Candida albicans, that consequently persist and recur in infections of the skin, nails and mucous membranes [7]. Most CMC patients also develop accompanying endocrine and inflammatory disorders that suggest an underlying deregulation of the inflammatory and immune responses [7]. 

In chronic inflammatory disorders there is a general over-activation of the immune system, the cause of which is often unknown. In all of these diseases, an increased number of infiltrated immune cells can be found in the inflamed tissues. Furthermore, increased expression of adhesion molecules on the endothelium can often be observed, although the adhesion molecules are expressed differentially in the various diseases. 

The activation of ai-adrenoreceptors is less studied in inflammatory disorders, since it does not seem to play a major role in immune functions (Hasko, 2001). 

In genetically susceptible individuals, ingestion of cereal prolamins from wheat, barley, rye, and possibly oats initiates an inflammatory disorder during which the small intestinal mucosa is damaged. This process is accompanied by malabsorption, activation of the intestinal immune system, and... 

Alanine nicotinoyl derivatives, (I), prepared by Porter (1) were effective as a and a4(37 integrin agonists/antagonists and used in the treatment of immune or inflammatory disorders. 

These form a large, unrelated group of disorders which underlie a variety of human diseases. The immune system is often involved with inflammatory disorders, demonstrated in both allergic reactions and some myopathies. Non-immune diseases with aetiological origins in inflammatory processes are thought to include cancer, atherosclerosis (Chapter 5) and ischaemic heart disease. 

S.C. Archibald etal, US Patent 6,329,362 (December 11, 2001) Assignee Celltech Therapeutics Limited Utility Treatment of Immune or Inflammatory Disorders... 

The SLe epitope is expressed on inflammation-induced acute phase proteins which serve as endogenous competitors for selectins and mediate a dampening of the immune response, returning inflammation to homeostasis [53]. Inhibitors of the selectins have been proposed to be useful therapies for treating inflammatory disorders including respiratory distress [54], hypersensitivity responses [55], and surgically induced myocardial ischemic reperfusion injury [56]. Animal studies have shown that the inhibition of selectin-carbohydrate interactions can alleviate these inflammatory responses. 

The serum iron concentration refers to the Fe " bound to serum transferrin and does not include the iron contained in serum as free Hb. The serum iron concentration is decreased in many but not aU patients with iron deficiency anemia and in chronic inflammatory disorders such as acute infection, immunization, and myocardial infarction (Table 31-4). Serum iron concentration diminishes especially in patients who are beginning to respond to specific hemathiic therapy for anemias of other causes such as treatment of pernicious anemia with cyanocobalamin. Acute or recent hemorrhage, including that caused by blood donation, results in low serum iron concentration. Serum iron con-... 

The current status of ongoing immunotherapeutic trials with levamisole in immune deficiency disorders, recurrent or chronic infections, chronic inflammatory diseases and cancer has been reviewed comprehensively. 2 Recent trials indicate that leveunisole provides significant therapeutic benefits in rheumatoid arthritis. 

Asthma is primarily a chronic inflammatory disorder of the airways of the lung characterized by T-helper cell type 2 (Th2)-lymphocyte-mediated immune response for which there is no known cure or primary prevention. 

Significant reductions in lymphocyte concentration (<1000/mm of blood) can be evident without apparent cause or in a variety of diseases, including acute inflammatory disorders, severe uremia, immune deficiency diseases such as systemic lupus erythematosus, chronic infections such as tuberculosis or human immunodeficiency virus (HIV) infection, malignancies, and connective tissue diseases. Lymphocytosis (>4000/mm ) may occur with mononucleosis, pertussis, measles, or chickenpox, and in lymphoid malignancies. A progressive increase in mature lymphocytes may be indicative of chronic lymphocytic leukemia. Increased levels of atypical lymphocytes may occur in patients with infections (e.g., mononucleosis, hepatitis, or cytomegalovirus), allergic reactions, or lymphomas." ... 

In conclusion, although hexachlorobenzene induces an auto-immune-like disorder in humans and rats, neoantigen formation and direct elicitation of autoreactive T cells are probably not involved. Rather, hexachlorobenzene, by activation of inflammatory cells such as macrophages, exacerbates autoimmunity above a level at which autoimmune phenomena and systemic inflammatory responses become apparent. This cascade of reactions is depicted in Figure 2 and illustrates the complexity of the etiology of immune derangements induced by hexachlorobenzene. 

Autoimmune haemolytic anaemia (AIHA). Acquired haemolytic anaemia mediated by autoantibodies against antigens on the organism s own red cell membrane. Autoimmune haemolytic anaemia may be idiopathic, secondary to lymphoproliferative, autoimmune (e.g. systemic lupus erythematosus), or chronic inflammatory disorders, postinfectious or drug-induced. See also -anaemia, cold autoantibody type, warm autoantibody type, -drug-induced immune haemolytic anaemia. 

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