Progress in understanding the pathogenesis of the anemia of chronic disease.

Improved understanding of the inflammatory response and the identification and characterization of the specific cytokines involved, as well as improved understanding of erythropoiesis, and the availability of recombinant human growth factors such as EPO, have greatly enhanced our appreciation of the pathogenesis of ACD by allowing development of a number of informative models for studying this syndrome. It appears that a variety of cytokines are involved in all aspects of the pathogenesis of ACD, from the inhibition of erythroid progenitors and EPO production to impairment of iron release. A schematic of the contributions of some of these cytokines to the development of ACD is shown in Fig 6. The exact biochemical mechanisms by which these effects occur is still to be determined. The progress outlined in this report has allowed us to develop a more precise understanding of the pathogenesis of this common and important clinical syndrome. In 1983, Hansen subtitled a review of ACD "A Bag of Unsolved Questions." Although this description is still accurate, our understanding of ACD has now developed to the point where we can offer a more defined subtitle: "A Bag of Cytokines."

Patterns of erythropoiesis and anaemia in leprosy.

A total of 128 leprosy patients were investigated for the morphological type of anaemia, the underlying disturbances in iron metabolism and patterns of erythropoiesis and other cytomorphological changes in the bone marrow. The anaemia was a mild to moderate degree in paucibacillary (PB) leprosy, while in multibacillary (MB) leprosy it was of a severe degree. Iron deficiency was observed in only a few patients. Impaired iron utilization as observed in a anaemia of a chronic disorder was a common finding in MB leprosy (41.7%) and more so in new cases (50%). Megaloblastic erythropoiesis was also more frequent in MB leprosy (45.2%) as compared to PB leprosy (16%), accounting for the severe degree of anaemia in the former type. In 17.2% of the total patients (MB, 21.4%; PB, 9%) both megaloblastic erythropoiesis and features of impaired iron utilization were observed in bone marrow. Disturbances in iron metabolism and erythropoiesis were also observed but to a lesser degree in patients receiving specific antileprosy treatment. Irrespective of the type of disease and duration of treatment, increasing frequency of acid-fast bacillia (AFB) positivity and granulomas was observed in the bone marrow with an increasing severity of anaemia.

Evaluation of phagocytic function in Mycobacterium lepraemurium infection.

Infection of mice with Mycobacterium lepraemurium caused significant functional alterations of the mononuclear phagocyte system. Accelerated clearance of sheep red blood cells was consistently demonstrated throughout the infection and the infected mice showed progressive anaemia. Infected mice showed an enhanced ability to limit growth of phagocytosed Listeria monocytogenes in spleens during the early stages of infection, whereas moribund leprous mice lost this ability. Autoradiography showed that uninfected Kupffer cells and splenic macrophages of moribund mice could still phagocytose Listeria, suggesting that MLM infection did not affect the capacity of Listeria to localize to macrophages but interfered in some way with subsequent killing of such bacteria. The possible mechanisms underlying these observations are discussed.

Complications of leprosy.

Leprosy is essentially a systemic disease and is a great "mimicker" of many other diseases. It affects apart from skin and peripheral nerves, haemopoietic, reticulo-endothelial and endocrine systems as well as eyes, bones and muscles.