Alpha-toxin and gamma-toxin jointly promote Staphylococcus aureus virulence in murine septic arthritis.
Septic arthritis is a common and feared complication of staphylococcal infections. Staphylococcus aureus produces a number of potential virulence factors including certain adhesins and enterotoxins. In this study we have assessed the roles of cytolytic toxins in the development of septic arthritis by inoculating mice with S. aureus wild-type strain 8325-4 or isogenic mutants differing in the expression of alpha-, beta-, and gamma-toxin production patterns. Mice inoculated with either an alpha- or beta-toxin mutant showed degrees of inflammation, joint damage, and weight decrease similar to wild-type-inoculated mice. In contrast, mice inoculated with either double (alpha- and gamma-toxin-deficient)- or triple (alpha-, beta-, and gamma-toxin-deficient)-mutant S. aureus strains showed lower frequency and severity of arthritis, measured both clinically and histologically, than mice inoculated with the wild-type strain. We conclude that simultaneous production of alpha- and gamma-toxin is a virulence factor in S. aureus arthritis. (+info)
Genetic control of experimental lyme arthritis in the absence of specific immunity.
Host genetics play an important role in determining resistance or susceptibility to experimental Lyme arthritis. While specific immunity appears to regulate disease resolution, innate immunity appears to regulate disease severity. Intradermal infection with Borrelia burgdorferi yields severe arthritis in C3H/He (C3H) mice but only minimal arthritis in BALB/c mice. Intradermal infection of immunodeficient C3H SCID mice also results in severe arthritis, but arthritis of only moderate severity in BALB/c SCID mice. In the present study, we examined immunodeficient recombinase-activating gene-knockout (RAG-1(-/-)) (RAG-) mice from resistant C57BL/6 (B6) and DBA/2 (DBA) mouse strains. B. burgdorferi-infected B6 RAG- and DBA RAG- mice had little or no ankle swelling, a low occurrence of inflammatory infiltrates in tibiotarsal joints, and low arthritis severity scores in comparison to RAG+ and RAG- BALB/c or C3H mice. Few differences in spirochete DNA levels in ankles of resistant and susceptible RAG- mice were seen. These data suggest that resistance to arthritis development following B. burgdorferi infection is not necessarily dependent on an acquired immune response and can occur despite the presence of high spirochete burden. Thus, genes expressed outside the specific immune response can be central regulators of experimental arthritis. (+info)
Osteonecrosis of the hip in sickle-cell disease associated with tuberculous arthritis. A review of 15 cases.
We report a study of 15 cases of tuberculous hips with sickle-cell disease who presented during 1991-1993. Although the osteonecrosis was long-standing, biopsy was nearly always required to reveal the more recent tuberculous infection. Management consisted of 6 months of anti-tuberculous chemotherapy with appropriate palliative surgery 5-8 weeks after the start of drug treatment. The operative techniques which we used are described. The results were good both post-operatively, and in 12 patients followed-up at an average of 3 years. We recommend this combined management for the treatment of secondary tuberculous infections of hips previously damaged by sickle-cell disease. (+info)
Longitudinal and cross-sectional variability in markers of joint metabolism in patients with knee pain and articular cartilage abnormalities.
OBJECTIVE: To determine the within- and between-patient variability in the concentrations of synovial fluid, serum and urine markers of joint tissue metabolism in a cohort of patients with knee pain and cartilage changes consistent with early-stage knee osteoarthritis. DESIGN: Samples of synovial fluid, serum, and urine were obtained from 52 patients on eight different occasions during 1 year, as part of a clinical trial in patients with cartilage abnormalities and knee pain. In joint fluid, aggrecan fragments were quantified by dye precipitation and enzyme-linked immunosorbent assay (ELISA), and matrix metalloproteinases-1 and -3, and tissue inhibitor of metalloproteinases-1 by sandwich ELISAs. In serum, keratan sulfate was quantified by ELISA. Type I collagen N-telopeptide cross-links in urine were determined by ELISA. RESULTS: The degree of cross-sectional variability in marker concentrations did not vary between the different sampling occasions, and did not differ between the periods of weeks 0 (baseline), 1-4 (treatment) and 13-26 (follow-up). Both between-patient and within-patient coefficients of variation varied for markers in different body fluid compartments, with the lowest variability for serum keratan sulfate, followed by urine type I collagen N-telopeptide crosslinks, and the highest for synovial fluid markers. For synovial fluid, aggrecan fragments showed the least variability, and matrix metalloproteinases the highest. One patient with septic arthritis showed a fivefold peak increase in joint fluid aggrecan fragment concentrations, while the concentration of matrix metalloproteinase-3 increased 100-fold. CONCLUSIONS: Molecular markers of joint tissue metabolism have been suggested as, for example, outcome measures for clinical trials of disease-modifying drugs in osteoarthritis. This report is the first to present data on between- and within-patient variability for such molecular markers in three different body fluid compartments in stable cohort of patients. The availability of such data enables calculations to determine the number of patients needed in prospective studies using these markers as outcome measures. (+info)
IL-1beta, IL-6 and TNF-alpha in synovial fluid of patients with non-gonococcal septic arthritis.
Interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are the main proinflammatory cytokines responsible for the inflammatory process and cartilage destruction of inflammatory arthropathies. The present study sequentially measured the concentrations of these cytokines and their proportions of detectable levels in the synovial fluid (SF) of 23 patients with non-gonococcal (GC) septic arthritis before and after treatment. Persistently high concentrations and proportions of IL-6 and TNF-alpha were found up to day 7 of treatment, while SF IL-1beta concentration declined significantly after day 7 (p = 0.036). SF IL-1beta and TNF-alpha correlated with each other significantly and with SF WBC counts (p < 0.01). Positive correlations between SF IL-1beta concentration and joint effusion (p < 0.01) and between SF TNF-alpha concentration and joint tenderness (p < 0.001) were observed. SF IL-1beta and TNF-alpha were significantly higher in patients with local complications of septic arthritis. In conclusion, high levels of IL-1beta, IL-6 and TNF-alpha were detected in SF of patients with non-GC septic arthritis. Only IL-1beta decreased significantly after day 7 of treatment, but IL-6 and TNF-alpha concentrations were persistently high. SF IL-1beta and TNF-alpha may be useful in predicting the outcome and complications of patients with this disease. (+info)
Slipped capital femoral epiphysis after septic arthritis of the hip in an adolescent: report of a case.
Septic arthritis of the hip must be managed promptly to avoid the serious complications associated with the condition. In the case reported here, the diagnosis was delayed and was complicated by a slipped capital femoral epiphysis. The patient, an adolescent boy previously in good health, presented with a 2-week history of hip pain and systemic illness. Septic arthritis was diagnosed and was managed by incision and drainage and antibiotic therapy. Two weeks later he presented with a subcutaneous abscess and a slipped capital femoral epiphysis, which was pinned in situ. There was a 2.5-cm leg-length discrepancy. Avascular necrosis of the femoral head subsequently developed leaving the boy with a permanent disability. (+info)
Gamma interferon and interleukin-10 gene expression in synovial tissues from patients with early stages of Chlamydia-associated arthritis and undifferentiated oligoarthritis and from healthy volunteers.
Genetically determined differences in interleukin-10 (IL-10) and gamma interferon (IFN-gamma) responses in mice correlate with clearance of Chlamydia pneumonitis infection. We measured the synovial expression of IL-10 and IFN-gamma and additional cytokine genes in patients who had recent-onset Chlamydia-associated arthritis (Chl-AA). IL-10 and IFN-gamma mRNA were relatively abundant in recent-onset Chl-AA. (+info)
Development of lyme arthritis in mice deficient in inducible nitric oxide synthase.
Nitric oxide (NO) is a powerful antimicrobial agent and an important regulatory molecule of the innate immune response. To determine if NO has a role in experimental Lyme disease, arthritis-resistant DBA/2J and arthritis-susceptible C3H/HeJ mice were bred to be genetically deficient for inducible NO synthase (iNOS). Following footpad injection of Borrelia burgdorferi, arthritis was similar between iNOS-deficient and control animals regardless of their genetic background. Histologic examination and arthritis severity scores of ankles revealed no differences in arthritis development between iNOS-deficient and control animals. Despite being deficient in a key antimicrobial agent, iNOS-deficient mice had tissue levels of B. burgdorferi similar to those in control mice. Thus, NO does not have a critical role in susceptibility to Lyme arthritis through tissue damage via an overexuberant inflammatory response, nor is it required in resistance through the clearance of spirochetes from tissues. (+info)