Murine models of anaemia of inflammation: extramedullary haematopoiesis represents a species specific difference to human anaemia of inflammation that can be eliminated by splenectomy.

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.

Achilles tendinosis is associated with sprouting of substance P positive nerve fibres.

OBJECTIVES: To identify and characterise nerve fibres and inflammatory alterations in painful Achilles tendinosis and thus gain evidence about the origin of pain in Achilles tendinosis. METHODS: The composition of 10 tendon samples from patients with a prior history of painful Achilles tendinosis and 10 samples from patients with spontaneously ruptured tendons but no previous pain was compared by immunohistochemistry and conventional histology. RESULTS: The presence of granulation tissue was shown in 8/10 cases of Achilles tendinosis. Nociceptive substance P (SP) positive nerve fibres were significantly increased, and an inflammatory infiltration comprising B and T lymphocytes was found. Additionally, small foci with iron positive haemosiderophages, indicating prior microtraumatic events, were found in 6/10 samples. None of the spontaneously ruptured tendons contained granulation tissue or haemosiderophages. Inflammatory infiltration in these patients consisted almost exclusively of granulocytes and SP positive nerve fibres were decreased. The density of sympathetic nerve fibres did not differ in the two conditions. CONCLUSION: Achilles tendinosis is associated with the presence of granulation tissue, haemosiderophages, and SP positive nerve fibres, which may transmit the clinically pertinent pain. Achilles tendinosis may be caused by repeated microtraumata with ensuing organisation that is accompanied by sprouting of nociceptive SP positive nerve fibres.