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.
Maloff
B L
BL
Medical Products Department, E. I. Du Pont de Nemours and Co., Inc., Wilmington, Delaware.
Shaw
J E
JE
Di Meo
T M
TM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D007375:Interleukin-1; D007975:Leukotriene B4 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase; D011994:Recombinant Proteins / Q000494:pharmacology; D013256:Steroids
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D011994:Recombinant Proteins; D013256:Steroids; D007975:Leukotriene B4; D009195:Peroxidase