IL-8 is involved in homologous TNFα-, but not in IL-1β-induced neutrophil infiltration in rabbits

Abstract.

Objective and Design: We examined the involvement of IL-8 in TNFα and IL-1β neutrophil infiltration, using homologous reagents.¶Subjects: Female New Zealand white rabbits (n = 211).¶Methods: After injection of TNFα (1 μg) or rrIL-1β (300 pg) into rabbit knee joints, the leukocyte influx and the production of IL-8 were estimated. Anti-TNFα mAb, rrIL-1Ra, and anti-IL-8 IgG (10 μg each) were administrated simultaneously with either TNFα or IL-1β.¶Results: Administration of TNFα or IL-1β induced IL-8 production; both of which peaked at 1 h after the injection. Maximum neutrophil infiltration induced by TNFα was inhibited by 38–56% by anti-IL-8 IgG, 22–43% by rrIL-1Ra, and 77–83% by anti-IL-8 IgG plus rrIL-1Ra. In contrast, maximum neutrophil infiltration induced by IL-1β was not inhibited by anti-IL-8 IgG whereas anti-TNFα mAb reduced the infiltration by 68–75%.¶Conclusions: The involvement of IL-8 in TNFα- and IL-1β-induced neutrophil infiltration is limited. Factor(s) other than IL-8 appear to function as major neutrophil chemoattractants.