Bradykinin diseases

It has been well documented that the anaemia of chronic disease, ACD, results in a lowering of various haematological parameters. Several mediators are involved, among them histamine, serotonin, bradykinin, prostaglandins and, as found more recently, cytokines and nitric oxide. ACD is a parameter of systemic autoimmune disorders. The severe inflammatory stimuli lead to several systemic changes, mediated by inflammation-associated cytokines, e.g. IL-6, IL-1 TNFa, TGF beta that regulate hepatic synthesis of the acute phase proteins. 

There is evidence that bradykinin may play a beneficial, protective role in certain cardiovascular diseases and ischemic stroke-induced brain injury. On the other hand, it has been implicated in cancer and some central nervous system diseases. 

Nearly all cells express kinin receptors that mediate the activities of both bradykinin and kallidin. The activation of these G-protein coupled receptors causes relaxation of venular smooth muscle and hypotension, increased vascular permeability, contraction of smooth muscle of the gut and airway leading to increased airway resistance, stimulation of sensory neurons, alteration of ion secretion of epithelial cells, production of nitric oxide, release of cytokines from leukocytes, and the production of eicosanoids from various cell types [11,12]. Because of this broad spectrum of activity, kinins have been implicated as an important mediator in many pathophysiologies including pain, sepsis, asthma, rheumatoid arthritis, pancreatitis, and a wide variety of other inflammatory diseases. Moreover, a recent report demonstrated that bradykinin B2 receptors on the surface of human fibroblasts were upregulated three-fold beyond normal in patients with Alzheimer s disease, implicating bradykinin as a participant in the peripheral inflammatory processes associated with that disease [13]. 

There is evidence that by acting on B2 receptors, bradykinin may play a beneficial, protective role in cardiovascular disease. Selective B2 agonists are available and have been shown to be effective in some animal models of human cardiovascular disease. These drugs may have potential for the treatment of hypertension and myocardial hypertrophy. 

H. Yasuda, Y. Kuriyamoto, and T. Nisbino. Plasma bradykinin concentration in patients with essential hypertension, effect angina and other cardiac diseases. Folia PhamacoL Jpn. 82.159 (1983). 

A. R, Joseph, K and Silverberg, M., Pathways for bradykinin formation and inflammatory diseases, J. Allergy Clin. Immunol. 109,195-209,2002 Shariat-Madar, Z., Mahdi, F, and Schmaier, A.H., Assembly and activation of the plasma kallikrein/kinin system a new interpretation, Int. Immunop-harmacol. 2, 1841-1849, 2002 Langbein, L. and Schweizer, J., Keratins of the human hair follicle, Int. Rev. Cytol. 243, 1-78, 2005 Gusterson,... 

Albumin solutions are manufactured from pooled plasma. They can contain other plasma constituents, such as heme compounds, prekalli-krein, endotoxins, bradykinin and bilirubin, in sufficient concentrations to cause clinical effects (Pulimood Park 2000). Some batches of human albumin have been shown to induce the expression of adhesion molecules on endothelial cells in vitro (Nohe et al 1999), which could result in activation of the immune system in vivo. Despite appropriate precautions during the manufacturing process, there is always a theoretical chance of transmission of disease with any biological product. 

Nitsch RM, Kim C, Growdon JH. 1998. Vasopressin and bradykinin regulate secretory processing of the amyloid protein precursor of Alzheimer s disease. Neurochem. Res. 23 807-14... 

Vascular endothelium and smooth muscle play important roles in regulating blood vessel tone and BP. These regulating functions are mediated through vasoactive substances that are synthesized by endothelial cells. It has been postulated that a deficiency in the local synthesis of vasodilating substances (e.g., prostacyclin and bradykinin) or excess vasoconstricting substances (e.g., angiotensin II and endothelin I) contribute to essential hypertension, atherosclerosis, and other diseases. 

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