Fibroblast growth-stimulatory activity released from human monocytes. The contribution of tumour necrosis factor

Human monocytes release fibroblast growth-stimulatory activity. In this study tumour necrosis factor (TNF) has been identified as a major contributor to the monocyte-derived fibroblast growth-stimulatory activity. A neutralizing monoclonal antibody (MoAb) against recombinant TNF (rTNF) inhibited growth of FS-4 fibroblasts and skin biopsy fibroblasts induced by monocyte supernatants, indicating that TNF was involved in the stimulation. Optimal growth of FS-4 fibroblasts was induced by monocyte supernatants at dilutions which contained TNF at a concentration between 1.6 X 10(-6) and 4.0 X 10(-5) micrograms/ml, less growth being induced at higher TNF concentrations. Contrary to this, no optimal concentration interval was found for rTNF, since increasing rTNF concentrations always resulted in increased growth stimulation. It also appeared that natural TNF in the monocyte supernatants induced growth at a much lower concentration than rTNF tested in the absence of monocyte supernatant.