Live Borrelia burgdorferi preferentially activate interleukin-1 beta gene expression and protein synthesis over the interleukin-1 receptor antagonist.

Abstract

Lyme arthritis is one of the few forms of chronic arthritis in which the cause is known with certainty. Because cytokines are thought to contribute to the pathogenesis of chronic arthritis, we investigated the effect of the Lyme disease spirochete, Borrelia burgdorferi, on the gene expression and synthesis of IL-1,8 and the IL-1 receptor antagonist (IL-lra) in human peripheral blood mononuclear cells. Live B. burgdorferi induced fivefold more IL-1l@ than IL-la and sevenfold more IL-1l8 than IL-lra; LPS or sonicated B. burgdorferi induced similar amounts of all three cytokines. This preferential induction of IL-1,B was most dramatic in response to a low passage, virulent preparation of B. burgdorferi vs. three high passage avirulent strains. No difference in induction of IL-lra was seen between these strains. The marked induction of IL-1iB was partially diminished by heat-treatment and abrogated by sonication; ILlra was not affected. This suggested that a membrane component(s) accounted for the preferential induction of IL-1i6. However, recombinant outer surface protein ,B induced little IL-1i6. burgdorferi-induced IL-1A6 mRNA showed biphasic elevations at 3 and 18 h. B. burgdorferi-induced IL-lra mRNA peaked at 12 h, whereas LPS-induced IL-lra mRNA peaked at 9 h. 8 synthesis increased in response to increasing numbers of spirochetes, whereas IL-lra synthesis did not. The preferential induction by B. burgdorferi of IL-1i8 over IL-lra is an example of excess agonist over antagonist synthesis induced by a microbial pathogen, and may contribute to the destructive lesion of Lyme arthritis. (J. Clin. Invest. 1992. 90:906-912.)

Pattern of Proinflammatory Cytokine Induction in RAW264.7 Mouse Macrophages Is Identical for Virulent and AttenuatedBorrelia burgdorferi

“…burgdorferi clinical isolates BL206 and B356 represent genotypes that are associated with distinctly different disease profiles in both humans and mice; BL206 infection results in severe, disseminated disease in C3H/HeJ mice, whereas B356 does not disseminate from the inoculation site (10,11 (Table I), which is consistent with previously reported findings connecting a higher IL-1␤/IL-1ra ratio with Lyme arthritis (39,40). While these experiments were in progress, a study was published that used array analysis to profile the global gene expression in the B. burgdorferi-infected joints of arthritis-susceptible C3H/ HeNCr mice and arthritis-resistant C57BL/6 mice (33).…”

A Pilot Study of the Predictive Value of Plasma Tumor Necrosis Factor α. and Interleukin 1β for Streptococcus pneumoniae Bacteremia in Febrile Children

“…8 -10.35. 36 This great disparity makes the comparison of our results with those of other studies difficult. Since most of the reports did not state the reproducibility or coefficients of variation of their levels, it is not possible to comment on them further.…”

Interleukin-1 Receptor Type I Gene-Deficient Mice Are Less Susceptible toStaphylococcus epidermidisBiomaterial-Associated Infection than Are Wild-Type Mice

“…Blocking of IL-1 activity by administration of IL-1R antagonist reduced tissue damage in experimental arthritis (41,42,49,55) and pancreatitis (43)(44)(45) and reduced mortality in experimental septic shock models (1,22,38). Additionally, IL-1 is assumed to have a role in bioincompatibility (9,10,12,16,18).…”