Increased vascular permeability and polymorphonuclear leucocyte accumulation in vivo in response to recombinant cytokines and supernatant from cultures of human synovial cells treated with interleukin 1.

Abstract

The inflammatory effects of intradermal injections of the human recombinant cytokines interleukin 1 (IL-1), granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor (TNF alpha) have been assessed in rabbit skin, and compared with the effects of a novel polymorphonuclear leucocyte (PMN)-stimulating activity (PSA) produced by IL-1-treated human synovial cell cultures. IL-1 (84 fmol) and GM-CSF (10 pmol) caused increases in vascular permeability with a delayed onset, as assessed by the dermal accumulation of intravenously-administered 125I-human serum albumin. These cytokines also stimulated extravascular accumulation of PMNs. In contrast, PSA-containing supernatant caused a more rapid and prolonged increase in vascular permeability and PMN accumulation. TNF alpha (84 fmol) was unable to stimulate either of these responses. The increases in vascular permeability and PMN accumulation following IL-1 administration in vivo may be a consequence of the local generation of PMN-stimulating activity by connective tissue cells, such as the activity produced by IL-1-treated synovial cell cultures that we have described.