Induction of membrane-associated interleukin 1 alpha (IL-1 alpha) by synergistic activation of human blood monocytes with interferon gamma and muramyl dipeptide analog

Abstract

Human blood monocytes isolated by centrifugal elutriation from healthy donors were tested for ability to produce membrane-associated IL-1 in response to activation stimuli such as various types of interferons (alpha, beta and gamma) and/or synthetic des-methyl muramyl dipeptide (norMDP). When monocytes were treated with norMDP or lipopolysaccharide (LPS) for 16 hr, they released IL-1 into their culture supernatant. When these activated monocytes were fixed with paraformaldehyde (PFA), they stimulated blastogenic responses of C3H/HeJ mouse thymocytes to PHA, suggesting that membrane-associated IL-1 could be induced by norMDP or LPS. Membrane-associated IL-1 was also found to be induced by the synergistic actions of suboptimal concentrations of rIFN-gamma and nor MDP, but not of rIFN-alpha A or rIFN-beta with norMDP. A specific anti-IL-1 alpha antiserum completely inhibited membrane-associated IL-1 activity, but did not affect the thymocyte-stimulating activity of fixed monocytes. IL-1 alpha was detected by fluorescence staining using the anti-IL-1 alpha antiserum on monocytes fixed after gamma IFN-gamma and norMDP. These results suggest that IFN-gamma may be important in expression of membrane-bound IL-1 alpha by the human blood monocytes responsible for regulation of immune responses in vivo.