Alkaline phosphatase (AP) is an ubiquitous enzyme in the human body that can be present in four isoforms. There are three tissue-specific AP isoforms, i.e. placental (PLAP), germ cell (GCAP) and intestinal (IAP) and one tissue-nonspecific isoform, TNSAP also called liver-bone-kidney (LBK) type. AP is thought to remove one of the two phosphate groups from the lipid A moiety of the Gram-negative bacterial endotoxin lipopolysaccharide (LPS), which results in inorganic phosphate (Pi) release and the formation of non-toxic dephosphorylated monophosphoryl LPS (MPLPS), thereby playing a role in the innate immune system. Detoxification of LPS by AP was observed in vitro only when incubated in a cell-based in vitro system as determined by a reduced production of cell-derived pro-inflammatory mediators. The fact that AP was unable to detoxify LPS in vitro in a cell-free environment indicates that accessory molecules are probably involved in the biological activity of AP. It was shown that presence of CD14 is necessary for AP to detoxify LPS, although the exact mechanism of action was not made clear. A disease suggested to be LPS-mediated is heart failure (HF). It is proposed that the observed inflammatory response in patients after HF, irrespective of etiology, is due to LPS translocation from the intestine into the circulation as a result of intestinal hypoperfusion. The positive effects of i.v. administration of AP on reducing the pro-inflammatory response and on angiotensin II (Ang II) formation after induction of one form of HF in mice, acute myocardial infarction (AMI), implicated that this enzyme might also be applicable to patients with other causes of HF. In addition to this, surgery under narcosis also leads to intestinal hypoperfusion resulting in inflammation comparable to that observed in HF patients. From this point of view, a Phase II clinical trial has currently started focusing on BIAP-mediated reduction of post-surgical ischemia-reperfusion damage in patients undergoing coronary artery bypass grafting (CABG). In contrast to AMI, which as its name already implies is a relatively acute disorder; ulcerative colitis (UC) is distinguished by chronic inflammation of the colon. There is growing evidence that UC results from an abnormal response of the host to commensal enteric bacteria or their components (e.g. LPS), which leads to activation of the mucosal immune system. The use of AP as an early treatment in dextran sulfate sodium (DSS)-induced acute colitis in mice, a preclinical model for testing the efficacy of treatments for UC, was investigated. Oral or rectal administration of AP resulted in a significant reduction of DSS-induced UC parameters, thereby showing for the first time intervention of AP in a chronic disease mediated by LPS. In conclusion, this thesis demonstrates that LPS-induced inflammation can be reduced by AP in an in vitro cell-based system as well as in an AMI and colitis experimental model in vivo. The current data, coupled with AP's safety record, justifies the development of AP for the treatment of LPS-mediated diseases in humans.