Induction, in vivo and in vitro, of macrophage membrane interleukin-1 by adjuvant-active synthetic muramyl peptides.
Recent evidence has shown that a membrane form of interleukin-1 (IL-1) serves as a necessary signal for antigen presentation, leading to T-cell activation. The synthetic immunostimulant muramyl dipeptide (MDP) is known to induce secretion of IL-1 and its adjuvant effect was found to be mediated through enhancement of T-helper cells. We have investigated the ability of MDP and 19 other adjuvant-active or -inactive MDP analogs and derivatives to induce membrane IL-1 in mouse peritoneal macrophages. Enhancement in vitro of membrane expression and secretion of IL-1 in fresh or aged cultures of macrophages was observed after stimulation with MDP or with adjuvant-active but not with adjuvant-inactive muramyl peptides. Administration in vivo of adjuvant-active doses of MDP or of any of 12 other active analogs induced high levels of macrophage membrane IL-1 detected by the lymphocyte-activating factor assay. This effect was not observed when 7 other adjuvant-inactive derivatives were used. Moreover, under conditions where MDP did not exert an adjuvant effect, this immunomodulator was found to be incapable of inducing the expression of macrophage membrane IL-1. These results demonstrate a very high correlation between the ability to induce membrane IL-1 and the adjuvant activity of muramyl peptides. The correlation was observed irrespective of other biological effects of the synthetic adjuvants such as pyrogenicity and/or anti-infectious activity.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006020:Glycopeptides / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D012995:Solubility; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D006020:Glycopeptides; D007375:Interleukin-1; D000119:Acetylmuramyl-Alanyl-Isoglutamine