Nitric oxide production during murine Lyme disease: lack of involvement in host resistance or pathology.
The murine model of Lyme disease was used to determine the role of inflammatory induced nitric oxide (NO) during infection by the spirochete Borrelia burgdorferi. The outer surface lipoproteins of B. burgdorferi are potent stimulators of inflammatory cytokines and NO production by cultured macrophages in vitro. The addition of NO to cultures of B. burgdorferi prevents growth, suggesting a protective role of NO for the infected host. NO is also a crucial effector in some models of arthritis. Therefore, the involvement of NO in controlling B. burgdorferi infection and its participation in pathological development of arthritis were investigated. Both mildly arthritic (BALB/c) and severely arthritic (C3H/HeJ) strains of mice systemically produced high levels of NO 1 week after infection with B. burgdorferi, as determined by urinary nitrate. NO production remained high throughout the infection in BALB/c mice, while in C3H/HeJ mice NO production returned rapidly to uninfected levels. The in vivo inhibitor of the NO synthase enzyme NG-L-monomethyl arginine (LMMA) was given to mice to investigate whether decreasing NO production would alter the course of disease. LMMA effectively blocked NO production in infected mice; however, there was no significant difference in arthritis development, spirochete infection of tissues, or production of specific antibody in LMMA-treated mice. These results indicate that B. burgdorferi is able to persist in the host even in the presence of high levels of NO. Furthermore, NO is not involved in the control of spirochete infection of tissues, nor is it involved in the development of arthritis. The potent activity of NO against intracellular pathogens and the in vivo resistance of B. burgdorferi to NO suggest that this organism is not located in an intracellular compartment during an essential portion of its infection of the mammalian host.
Seiler
K P
KP
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Vavrin
Z
Z
Eichwald
E
E
Hibbs
J B
JB
Weis
J J
JJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D005260:Female; D008193:Lyme Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis*; D013045:Species Specificity; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine