Inflammation, Vol. 28, No. 3, June 2004 ( C  2004) Inflammation Induced by Inoculation of the Joint with Candida albicans Martin Yordanov, 1 Svetla Danova, 2 and Nina Ivanovska 1,3 Abstract—In humans Candida albicans is the most frequently isolated opportunistic fungal pathogen. In immunocompromized host the balance with the commensal fungus easily turns to life-threatening disseminated infection. The asymptomatic Candida persistence in organs and the recurrent infections suggest continuous circulation of yeast cells and their degradation products. Under certain conditions, joints might become one of the infectious sites. More easily a reactivation and destructive process can be provoked in individuals with established arthritis. We have investigated the joint inflammation caused by inoculation of the paw with live C. albicans, in intact mice and mice with collagen-induced arthritis (CIA). The results demonstrate that C. albicans infection when localized into the joints caused rapidly progressing septic arthritis. The effect was associated with a strong swelling, a rapid influx of polymorphonuclear (PMN) cells, and an elevated secretion of TNF-α and IFN-γ by lymph node cells. Joint infection exacerbated the established CIA which correlated with an increased level of anti-collagen antibodies. KEY WORDS: Candida albicans; septic arthritis; collagen-induced arthritis. INTRODUCTION The relationships between infections and rheumatic diseases have been an object of recent investigations in the light of Th1/Th2 balance (1, 2). Although reactive arthritis is often associated with bacterial infections of gastrointestinal or urogenital tracts (3) it is not clear whether bacteria causes or exacerbates arthritis in hu- mans. Epidemiologic studies show that despite antibiotic treatment, inflammation and arthritic joint symptoms continue (4). It is supposed that the commensal flora of the gut induces a tolerant state to self-antigens, while the shift to Th1 response and an increased production 1 Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 113 Sofia, Bulgaria. 2 Department of Genetics, Institute of Microbiology, Bulgarian Academy of Sciences, 113 Sofia, Bulgaria. 3 To whom correspondence should be addressed at Department of Im- munology, Institute of Microbiology, Bulgarian Academy of Sci- ences, 26 G. Bonchev St., 1113 Sofia, Bulgaria. E-mail: nina@ microbio.bas.bg of proinflammatory cytokines during severe systemic infections can provoke arthritic process in predisposed individuals (5). Candida albicans is the most frequently isolated opportunistic fungal pathogen. In immuno- compromized individuals the balance between the host and the commensal readily turns to severe infection. Studies in mice have shown that the protective response to C. albicans is due to the prevalence of Th1 cytokines and the relative decrease of Th2 cytokines (6, 7). Early in infection the production of TNF-α is essentially high (8) and at the same time TNF-α is one of the major proinflam- matory cytokines in arthritis. Experimental arthritis as a consequence of intravenous inoculation with C. albicans has been induced in rats (9). Altogether, these data raised the question whether C. albicans might play a role in the pathogenesis of arthritis. The purpose of the present experiments was to estimate the ability of the yeast to provoke septic form of arthritis and its effect in mice with established collagen-induced arthritis. After inoculation of the paw with C. albicans, the development of swelling, histopathologic changes, and yeast elimination were 127 0360-3997/04/0600-0127/0 C  2004 Springer Science+Business Media, Inc.