The development of experimental Lyme arthritis has been correlated with the expression of a number of chemokines and cytokines, however, none of these have been measured directly from the arthritic joint. We examined the temporal expression of IL-1β, IL-4, IL-6, IL-10, IL-12p70, GM-CSF, IFN-γ, TNF-α, macrophage inflammatory protein-2, KC, macrophage inflammatory protein-1α, and monocyte chemoattractant protein-1 directly from the tibiotarsal joint in arthritis-resistant C57BL/6 (B6) and -susceptible C3H/He (C3H) mice. Only the chemokines KC and monocyte chemoattractant protein-1 were differentially expressed in joints of B6 and C3H mice and correlated with the development of Lyme arthritis. Infection of CXCR2−/− mice on either genetic background resulted in a significant decrease in the development of pathology, although infection of CCR2−/− mice had little or no effect. Neutrophils in CXCR2−/− mice were marginalized within blood vessels and could not enter the joint tissue. These results suggest that chemokine-mediated recruitment of neutrophils into the infected joint is a key requirement for the development of experimental Lyme arthritis.

Recently, we demonstrated that blocking the entry of neutrophils into Borrelia burgdorferi-infected joints in mice deficient in the chemokine receptor CXCR2 prevented the development of experimental Lyme arthritis. Neutrophils were marginalized in blood vessels at the site of infection but could not enter the joint tissue. In the present study, we treated both genetically arthritis-resistant DBA/2J (DBA) and arthritis-susceptible C3H/HeJ (C3H) mice with the neutrophil-depleting monoclonal antibody RB6-8C5 (RB6) to determine the effect on arthritis development. Surprisingly, both DBA and C3H mice treated with RB6 developed arthritis at 1 week postinfection, approximately 1 week earlier than the control-treated C3H mice. The early development of arthritis in the RB6-treated mice was accompanied by an influx into the joints of cells with ring-shaped polymorphonuclear leukocyte (PMN) cell morphology that were negative for the Gr-1 neutrophil maturation marker. RB6 treatment of mice also resulted in increased numbers of B. burgdorferi cells in the joints at 7 days postinfection and earlier expression of the chemokines KC and monocyte chemoattractant protein 1 in the joints compared to control-treated animals. Together, these results suggest that recruitment of neutrophils or PMN-like cells into an infected joint is a key requirement for Lyme arthritis development and that altered recruitment of these cells into the joints of arthritis-resistant mice can exacerbate the development of pathology.

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Background It is assumed that moderate exercise may improve resistance to infection and reduce inflammation, but there are limited data to support this assumption in an infection model. Methods BALB/cJ mice were assigned to the following groups: no exercise (NON-EX), 1 session of acute exercise (A-EX), or chronic exercise for ~3.5 months (C-EX). Mice were infected with influenza (C-EX mice infected at rest; A-EX mice infected 15 min after exercise). Results C-EX mice demonstrated the lowest severity of infection, assessed by body weight loss and food intake. There was less virus in the lungs at day 5 after infection in C-EX and A-EX mice compared with NON-EX mice (P = .02) and less virus at day 2 after infection only in C-EX mice (P = .07). Soon after infection (day 2), interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1β, and tumor necrosis factor α in the bronchoalveolar lavage (BAL) fluid were lower in C-EX and A-EX than in NON-EX mice. At day 5 after infection, the BAL fluid from C-EX (but not A-EX) mice had less IL-6, interleukin 12p40, granulocyte colony-stimulating factor, keratinococyte-derived chemokine, and MCP-1 than that from NON-EX mice. A trend toward reduced immunopathologic response was found in C-EX mice. Conclusions Chronic exercise resulted in reduced symptoms, virus load, and levels of inflammatory cytokine and chemokines. Acute exercise also showed some benefit, which was limited to the early phase of infection.