NOD mice have a severly impaired ability to recruit leukocytes into sites of inflammation

The accumulation of macrophages (MΦ) and dendritic cells (DC) in the pancreas plays a crucial role in the pathogenesis of autoimmune diabetes. We studied the recruitment of monocytes, MΦ and DC to sites of inflammation, i.e. the peritoneal cavity and a subcutaneously elicited air pouch in the NOD mouse model of autoimmune diabetes. The leukocyte recruitment was studied from 1 to 7 days after injection of thioglycollate (peritoneum), C5a (peritoneum, air pouch), CCL2 and CCL3 (air pouch). C57BL/6 and BALB/c mice served as controls. Morphological and flow cytometric analysis of the recruited cells was performed, IL‐1β, TNF‐α, IL‐6, IL‐12 and IL‐10 in exudates measured, and in vitro CCL2‐chemotaxis of exudate MΦ (Boyden chamber) determined. NOD mice were strongly impaired in the recruitment of MΦ, DC, monocytes, and granulocytes. Chemokine‐injected air pouches of NOD mice showed an increased IL‐10 and a decreased IL‐1β level, while the other cytokines were normally or very lowly expressed. In addition, NOD exudate MΦ displayed an impaired in vitro CCL2‐induced migration. Our data show that NOD mice have an impaired ability to recruit leukocytes into sites of inflammation elicited in the peritoneum and the air pouch. A raised IL‐10/IL‐1β ratio at these sites and a deficient migratory capacity of NOD monocytes are important determinants in this impairment.