Murine Models of Anaemia of Inflammation: Extramedullary Haematopoiesis Represents a Species Specific Difference to Human Anaemia of Inflammation That Can Be Eliminated by Splenectomy

Abstract

In contrast to humans, mice physiologically exhibit extramedullary haematopoiesis in the spleen. In spite of this crucial species specific difference not much is known about the contribution of extramedullary haematopoiesis to overall erythropoiesis in models of anaemia of inflammation (AI). The objective of this study is to characterize murine AI with respect to extramedullary haematopoiesis and to develop a model more closely resembling human AI. Three different models of AI [caecal ligation and puncture (CLP), collagen induced arthritis (CIA) and DSS induced chronic colitis (DSSC)] were characterized with respect to red blood parameters, iron metabolism and extramedullary haematopoiesis. Arthritic animals were splenectomised to prevent extramedullary haematopoiesis. Anaemia caused by systemic inflammation was found in all three models. Splenic extramedullary haematopoiesis was markedly increased as reflected by increment in spleen weights and increase of the red pulp resulting in increased reticulocyte counts. Splenectomised arthritic animals did not show increased reticulocyte counts indicating that most of the reticulocytes were produced in the spleen. Our results demonstrate that murine AI differs from human AI with respect to increased splenic extramedullary haematopoiesis. Our data demonstrate that induction of AI in splenectomised mice represents a good way to model human AI.