CARRAGEENAN-INDUCED ACUTE-INFLAMMATION IN THE MOUSE AIR POUCH SYNOVIAL MODEL - ROLE OF TUMOR-NECROSIS-FACTOR

WE used the mouse air pouch model of inflammation to study the interac tion between cytokines, prostaglandin E(2) (PGE(2)) and cell migration during the various phases of acute local inflammation induced by carr ageenan. In serum, the levels of interleukin 1 (IL-1), interleukin 6 ( IL-6), tumour necrosis factor (TNF), serum amiloid-A (SAA) and Fe++ we re never different from controls, indicating that no systemic inflamma tory changes were induced Locally the exudate volume and the number of leukocytes recruited into the pouch increased progressively until 7 d ays after carrageenan. The same was true for PGE(2) production. We cou ld not measure IL-1 but the production of IL-6 and TNF reached a maxim um after 5-24 h then quickly decreased Anti-TNF antibodies inhibited c ell migration by 50% 24 h after treatment. Pretreatment with interleuk in 10 (IL-10) inhibited TNF production almost completely and cell migr ation by 60%. Carrageenan-induced inflammation was modulated by anti-i nflammatory drugs. Pretreatment with dexamethasone (DEX) or indomethac in (INDO) inhibited cell migration and reduced the concentration of TN F in the exudate. Production of PGE(2) or vascular permeability did no t correlate with the number of cells in the pouch. Local TNF seems to play an important role in this model, particularly for leukocyte migra tion in the first phase of the inflammatory process. In conclusion, th e air pouch seems to be a good model for studying the regulation of th e early events of local inflammation, particularly the role of cytokin es and cell migration.