Evidence that neutrophil accumulation induced by interleukin-1 requires both local protein biosynthesis and neutrophil CD18 antigen expression in vivo.

1. Mechanisms involved in neutrophil accumulation induced by intradermal injection of interleukin-1 (IL-1) in the rabbit were investigated using intravenously-injected 111In-labelled neutrophils. C5a des Arg, N-formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4) were included for comparison. 2. Local inhibition of protein biosynthesis in the skin using actinomycin-D or cycloheximide blocked 111In-neutrophil accumulation induced by IL-1, but not that induced by the other mediators. 3. Actinomycin-D and cycloheximide had no effect on local plasma protein leakage induced by intradermally-injected C5a des Arg, or that induced by zymosan. 111In-neutrophil accumulation induced by zymosan was, however, partially suppressed. 4. A monoclonal antibody, MoAb 60.3, recognising neutrophil surface CD18 antigen, was preincubated with 111In-neutrophils before intravenous injection. This pretreatment did not affect circulating numbers of radiolabelled cells, but it inhibited their accumulation in response to IL-1, C5a des Arg and the other mediators. 5. The results suggest that neutrophil accumulation induced by IL-1, but not the other mediators, requires local protein biosynthesis, probably in the microvascular endothelium. Neutrophil accumulation to IL-1 and the other mediators appears to require neutrophil surface antigen, CD18. The inflammatory response to zymosan may be mediated by both endogenous C5a des Arg and IL-1.