Identification of a common class of high affinity receptors for both types of porcine interleukin-1 on connective tissue cells

Abstract

Interleukin-1 (IL-1) is the name given to the polypeptides produced by activated mononuclear phagocytes which were originally defined as lymphocyte activating factors (LAF)¹. Administration of IL-1 in vivo causes fever² and synthesis of acute phase proteins³. In vitro they have been shown to cause cartilage and bone resorption^4–7, and to stimulate fibroblasts and chondrocytes to make prostaglandins and latent collagenase^4,8. IL-1 has therefore been proposed to be an important inflammatory mediator⁹ and may be involved in the destruction of cartilage and bone that is a feature of rheumatoid arthritis and other inflammatory diseases of joints. We therefore looked for IL-1 receptors on connective tissue cells which might be targets for therapeutic intervention. Here we report the iodination, to high specific activity and with retention of full biological potency, of the two types of natural porcine IL-1. These ligands have been used to demonstrate high affinity dissociation constant (∼10⁻¹⁰M) specific binding sites on pig chondrocytes and synovial fibroblasts, human dermal fibroblasts and murine osteoblasts (3,000–5,000 sites per cell). Most interestingly, the two different II-1 proteins show a similar affinity for a common class of receptors.