Mononeuropathy multiplex in rhesus monkeys with chronic lyme disease

Abstract

Peripheral neuropathy is a recognized but poorly understood manifestation of Lyme disease. We performed serial electrophysiological studies on 8 rhesus monkeys chronically infected with the JD1 strain of Borrelia burgdorferi and compared the results with those of similar studies on 10 uninfected control monkeys. Four infected and 2 uninfected animals underwent sural nerve biopsy. Five of the infected and 1 of the uninfected animals also had postmortem neuropathological examinations. Altogether, 5 of the infected monkeys demonstrated primarily axonal-loss-variety multifocal neuropathies. Only one nerve lesion exhibited findings compatible with demyelination. Pathologically, peripheral nerve specimens showed multifocal axonal degeneration and regeneration and occasional perivascular inflammatory cellular infiltrates without vessel wall necrosis. Free spirochetal structures were not seen, but several macrophages exhibited positive immunostaining with a highly specific anti-B. burgdorferi, 7.5-kd lipoprotein monoclonal antibody. In the infected animals, serial analysis of serum antibodies to B. burgdorferi showed increasing numbers of IgG specificities and new IgM specificities, suggesting persistent infection. Thus, peripheral neuropathy in the form of a mononeuropathy multiplex develops frequently in rhesus monkeys chronically infected with B. burgdorferi. The pathogenesis of these nerve lesions is not yet known, but our studies suggest an immune-mediated process perhaps driven by persistent infection with B. burgdorferi.

Interleukin-10 Alters Effector Functions of Multiple Genes Induced by Borrelia burgdorferi in Macrophages To Regulate Lyme Disease Inflammation

“…Invasion of the mammalian host with spirochetes results in the activation of inflammatory pathways that lead to the release of inflammatory mediators and an influx of inflammatory cells that result in many of the clinical manifestations of Lyme disease (9,(42)(43)(44)79). Manifestations of the disease include, among others, acute or chronic arthritis, carditis, and neuroborreliosis (23,31,75,79,93). The inflammatory immune response is of crucial importance for the early containment of infection but at the same time has the potential to result in immunopathology.…”

Interleukin-10 Anti-Inflammatory Response toBorrelia burgdorferi, the Agent of Lyme Disease: a Possible Role for Suppressors of Cytokine Signaling 1 and 3

“…The spirochete can invade multiple organs (4, 59) and persist in them for a long time (47,65). Spirochetal persistence in the tissues has been associated with severe pathology (14,21,65) and both acute and chronic inflammatory conditions (50,59). Numerous studies have shown that B. burgdorferi and its lipoproteins can induce in a variety of cell types the release of proinflammatory cytokines, such as interleukin…”

“…The spirochete can invade multiple organs (4,59) and persist in them for a long time (47,65). Spirochetal persistence in the tissues has been associated with severe pathology (14,21,65) and both acute and chronic inflammatory conditions (50,59). Numerous studies have shown that B. burgdorferi and its lipoproteins can induce in a variety of cell types the release of proinflammatory cytokines, such as interleukin-1␣ (IL-1␣) (10), IL-1␤ (45), 23,45,54,55,64), IL-8 (10), IL-12 (30,45,58), tumor necrosis factor alpha (TNF-␣) (8,45,53,54,55,58,64), gamma interferon (IFN-␥) (22,23,24), IL-17 (35), granulocyte-macrophage colony-stimulating factor (GM-CSF) (67), and IL-18 (30).…”

Autocrine and Exocrine Regulation of Interleukin-10 Production in THP-1 Cells Stimulated withBorrelia burgdorferiLipoproteins

“…Infection may involve multiple organs (3,42) and may persist in certain tissues for prolonged periods of time (35,48). Spirochetal persistence in the tissues has been associated with severe pathology (9,16,48) and both acute and chronic inflammatory conditions (37,42). B. burgdorferi lacks lipopolysaccharide (LPS) (43), but its genome contains no fewer than 150 genes coding for putative lipoproteins (18); this amounts roughly to 11% of its genome coding capacity.…”