IL-1 dependent model of inflammation mediated by neutrophils

Interleukin-1 (IL-1) mediates a number of immunologic and physiologic responses associated with inflammation. A new model to monitor the primary effects of IL-1 and potential inhibitors on inflammation has been developed, which involves unilateral injection of 300 U of highly purified recombinant human IL-1 in mouse ears. Ear thickness of IL-1 injected ears increased 7-10-fold 24 hr posttreatment, concomitant with a corresponding increase in myeloperoxidase activity, suggesting that neutrophil influx contributes to this response. Administration of nonsteroidal antiinflammatory drugs did not influence the IL-1 effect in vivo. Inhibition of phospholipase A2 activity ameliorated the IL-1 stimulated inflammation; treatment with 10 mg/kg dexamethaxone eliminated approximately 80% of increased myeloperoxidase activity compared to control values. This model provides a well-defined in vivo assay with which to quantify the systemic effects of compounds capable of altering the activity of IL-1, and the data suggest that this mechanism may explain the unique efficacy of steroids as antiinflammatories.