Studies on early events of Borrelia burgdorferi-induced cytokine production in immunodeficient SCID mice by using a tissue chamber model for acute inflammation.
Lyme arthritis, one of the common features of Borrelia burgdorferi infection in the human, is associated with the production of various monocyte derived cytokines. To investigate the expression and regulation of cytokines during the acute phase of spirochete induced inflammation, a perforated Teflon chamber was implanted under the dorsal skin of severe combined immunodeficiency (SCID) and immunocompetent co-isogenic C.B-17 mice. The histology of the surrounding chamber tissue exhibited sterile inflammation with several features reminiscent of an inflamed synovium, i.e. infiltration of polymorphonuclear and mononuclear cells, fibroblast-like cells and neovascularization. The experimental inoculation of Borrelia burgdorferi into the chamber resulted in the production of TNF-alpha, IL-1 and IL-6 into the chamber exudate, in both the immunodeficient, disease susceptible SCID and the immunocompetent, disease resistant C.B-17 mice. Peak levels of TNF-alpha were reached at 2 hours and of IL-1 and IL-6 at 6 hours after infection; by 24 hours, cytokine levels were only marginal (IL-1, IL-6) or non-detectable (TNF-alpha). Experimental infection by s.c. injection distant from the tissue chamber led to colonization of the spirochetes into the chamber, suggesting a tropism of the bacteria for this tissue. Thus, this model provides a system for studying acute events of Borellia burgdorferi induced cytokine regulation in a complex cellular, synovium-like environment that the bacterium encounters in vivo.
Hurtenbach
U
U
Sandoz Ltd., Basel, Switzerland.
Museteanu
C
C
Gasser
J
J
Schaible
U E
UE
Simon
M M
MM
D000208:Acute Disease; D000818:Animals; D001170:Arthritis, Infectious / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005122:Exudates and Transudates / Q000166:cytology; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008193:Lyme Disease / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009504:Neutrophils / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha