IL-8 IS INVOLVED IN HOMOLOGOUS TNF-ALPHA-INDUCED, BUT NOT IN IL-1-BETA-INDUCED NEUTROPHIL INFILTRATION IN RABBITS

Objective and Design: We examined the involvement of IL-8 in TNF alpha and IL-1 beta neutrophil infiltration, using homologous reagents. Sub jects: Female New Zealand white rabbits (n = 211). Methods: After inje ction of TNF alpha (1 mu g) or rrIL-1 beta (300 pg) into rabbit knee j oints, the leukocyte influx and the production of IL-8 were estimated. Anti-TNF alpha mAb, rrIL-1Ra, and anti-IL-8 IgG (10 mu g each) were a dministrated simultaneously with either TNF alpha or IL-1 beta. Result s: Administration of TNF alpha or IL-1 beta induced IL-8 production; b oth of which peaked at 1 h after the injection. Maximum neutrophil inf iltration induced by TNF alpha was inhibited by 38-56% by anti-IL-8 Ig G, 22-43% by rrIL-1Ra, and 77-83% by anti-IL-8 IgG plus rrIL-1Ra. In c ontrast, maximum neutrophil infiltration induced by IL-1 beta was not inhibited by anti-IL-8 IgG whereas anti-TNF alpha mAb reduced the infi ltration by 68-75%. Conclusions: The involvement of IL-8 in TNF alpha- and IL-1 beta-induced neutrophil infiltration is limited. Factor(s) o ther than IL-8 appear to function as major neutrophil chemoattractants .