The highest prevalence of anemia exists in the developing world where its causes are multi-factorial. Anemia is responsible for significant morbidity and mortality, particularly in less developed countries (LDCs). Understanding causes of anemia and potential mechanisms are crucial to our ability to intervene to reduce this burden. In the past decade, our understanding of the etiology and mechanisms of anemia in LDCs has advanced significantly. This review will focus on recent advances in our understanding of the burden of anemia in specific sub-groups, the causes and mechanisms of anemia, and consequences of anemia for the human host.

, we have identified the enzyme that catalyzes the -1 and -2 oxidation of LTB 4 in mouse myeloid cells as CYP4F18. As determined by mass spectrometry, this enzyme catalyzes the conversion of LTB 4 to 19-OH LTB 4 and to a lesser extent 18-OH LTB 4 . Inhibition of CYP4F18 resulted in a marked increase in calcium flux and a 220% increase in the chemotactic response of mouse PMN to LTB 4 . CYP4F18 expression was induced in bone marrow-derived dendritic cells by bacterial lipopolysaccharide, a ligand for TLR4, and by poly(I⅐C), a ligand for TLR3. However, when bone marrow-derived myeloid dendritic cells trafficked to popliteal lymph nodes from paw pads, the expression of CYP4F18 was down-regulated. The results identify CYP4F18 as a critical protein in the regulation of LTB 4 metabolism and functional responses in mouse PMN and identify it as the functional orthologue of human PMN CYP4F3A.How polymorphonuclear leukocytes (PMN), 2 macrophages, and dendritic cells (DC) control the initiation and amplification of innate and adaptive immune responses is a critical question, and the 5-lipoxygenase product of arachidonic acid metabolism leukotriene B 4 (LTB 4 ) is central to the amplification process. LTB 4 is equal to the most potent chemoattractant known for myeloid cells (1-6) and is synthesized from arachidonic acid by the action and interactions of 5-lipoxygenase, the five-lipoxygenase-activating protein, and leukotriene A 4 hydrolase (7). LTB 4 mediates its activity in these cells via the high affinity G proteincoupled receptor BLT1 (8 -10).LTB 4 has been implicated in the pathogenesis of multiple inflammatory diseases including inflammatory bowel disease (11-14), glomerulonephritis (15, 16), allograft rejection in kidney transplant models (17, 18), and cardiac allograft rejection (19). Studies with knock-out mice for the five-lipoxygenase-activating protein combined with LTB 4 receptor antagonists have supported a role for LTB 4 in murine collagen arthritis (20), in the EAE model of multiple sclerosis (21), and in mediating a primate model of asthma (22). In atherosclerosis, 5-lipoxygenase has been identified as a risk gene in a mouse model, and 5-lipoxygenase-rich cells have been identified in atheroscleotic plaques of mice and humans (23, 24). Furthermore, a protein closely related to CYP4F3A, presumably a mouse member of the CYP4F family, was strongly induced in foam cells in mice (23). Blockade of BLT1 has been associated with decreased progression of atherosclerosis in APOE1Ϫ/Ϫ mice (25,26). Understanding the molecular basis of LTB 4 signal termination is critical to elucidating how animals control the amplitude of inflammation in LTB 4 -dependent settings.There are two general cellular mechanisms that have the potential to terminate the responsiveness to LTB 4 and to all other chemoattractant molecules for G protein-coupled receptors. The first is the enzymatic metabolism of ligands. The second is receptor desensitization, which is based on G protein-coupled receptor kinases and ␤-arrestin (27, 28). The desensi...