Pathophysiology of Bik

Bik is normally elevated during pregnancy to prevent premature labor [4]. Clinically, Bik has been administered as a therapeutic agent to prevent premature labor. The expression of Bik decreases in preparation for labor as the quiescent uterine smooth muscle switches to a state of contractility. The mechanism by which Bik prevents premature labor is partly due to an inhibition of smooth muscle Ca2+ influx [83, 84]. 

Inflammation is a common component associated with sepsis, meningitis, as well as respiratory tract, urinary tract, viral, and bacterial infections (Table 1). Bik is elevated during bacterial or viral infection. The presence of urinary Bik correlates well with standard urinalysis tests for urinary tract infections [20]. Endotoxins released from infectious pathogens induce inflammation and immune cell activation. Macrophages release interleukins and cytokines (IL-1, IL-6, IL-12, IL-15, IL-18, TNF-a) on exposure to lipo-polysaccharide (LPS) and lipoteichoic acid (LTA) endotoxins. These cytokines act as a chemotactic factors causing immune cell migration to the site of the infection followed by activation and release of proteases. Cytokines also induce increased vascular permeability in the endothelial. Bik suppresses further cytokine release by protease and intern additional migration and activation of immune cells. Additionally, a stabilization of the immune cell membrane prevents further release of proteases [4]. 

Acute inflammation Acute viral infections Kidney stones Preeclampsia Surgical trauma Transplant rejection Myocardial infarction CHF Pancreatitis Trauma 

Cancer Breast Colon Esophagus Leukemia, all types Lymphoma, all types Multiple myeloma Ovarian cancer Pancreas Stomach 

Chronic inflammation Acute coronary syndrome Crohn s disease Emphysema Hepatitis Inflammatory bowel disease Rheumatoid arthritis 

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Bikunin (Bik), a peptide excreted in the urine, is one of the primary inhibitors of the trypsin family of serine proteases. This peptide plays a key role in inflammation and innate immunity because of its two Kunitz-type binding domains [1, 2], Bik suppresses proteolytic activity in a variety of tissues and can also exert localized anti-inflammatory effect [3-5], Inflammation is an important indicator of infection, cancer, and tissue injury in acute and chronic states. In acute inflammation, fluids and plasma components accumulate in the affected tissues due to vascular dilation. Subsequent activation of platelets and increased presence of immune cells occur during repair. Long-standing inflammation may be present before the disorder is identified. Due to its inhibitory role and potential use as an early marker of inflammation, we will review the synthesis, structure, pathophysiology of Bik as well as the various approaches for its measurement in this chapter. 

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