A role for interleukin-1 in the pathogenesis of Lyme disease.
Interleukin-1 (IL-1) is the major immunoregulatory molecule produced by macrophages in response to a variety of environmental insults including chemicals, phagocytosis, bacteria, and bacterial products. Macrophages stimulated by Borrelia burgdorferi produced large quantities of IL-1 when spirochetes were added to macrophages at a ratio of 10 spirochetes per macrophage. The release of IL-1 was dose dependent: a single spirochete per macrophage was sufficient to produce significant quantities of IL-1. Spirochetal lipopolysaccharide was not required for this activity in that polymyxin B in the spirochete-macrophage culture had no effect on IL-1 production. Normal murine fibroblasts cultured with this IL-1 were shown to have an increased rate of DNA synthesis and an increase in secreted collagenase. IL-1 was found in joint fluids from Lyme disease patients. When IL-1 was injected intradermally into the backs of rabbits, the injection sites became indurated, erythematous, and warm to the touch after 4 hrs and annular lesions much like those of erythema chronicum migrans were seen in some animals after 24 hrs. B. burgdorferi is a powerful inducer for IL-1 in vitro, and it is reasonable to presume that it acts similarly in Lyme disease patients. Our results suggest that IL-1 in turn, may play a role in many of the clinical manifestations of Lyme disease.
D000818:Animals; D001898:Borrelia / Q000276:immunology*; D002460:Cell Line; D005347:Fibroblasts; D006801:Humans; D007249:Inflammation / Q000209:etiology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology; D008193:Lyme Disease / Q000209:etiology* / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D011817:Rabbits; D013582:Synovial Fluid / Q000032:analysis
D007375:Interleukin-1; D008070:Lipopolysaccharides