A Possible Interconnection of Cholesterol Overloading and Phagocytic Activityof the Monocytes in the Prone to Rheumatoid Arthritis Individuals

Abstract

Background: The abnormalities of lipid metabolism were demonstrated in the individuals, who later develop rheumatoid arthritis (RA). Trivial infections are known to contribute to atherosclerosis. We showed that first degree relatives of RA patients suffer from frequent and lingering trivial infections. The interconnection between the disturbance of lipid metabolism and the increased trivial infection burden is hypothesized in this group. Mononuclear phagocytes (MP) are the important players in RA pathogenesis, antiinfectious defense and atherosclerosis. The aim was to investigate the interconnection between the involvement of MPs in cholesterol metabolism, their phagocytic activity and the burden of trivial infections in the RA patients, their relatives and healthy individuals without autoimmune diseases in family history. Methods: The following parameters were studied: intracellular cholesterol content (colorimetric), membrane cholesterol content and microviscosity (fluorescent), engulfment and digestion (radioisotope); reactive oxygen species generation (chemiluminescence). Results: In relatives MPs and their cell membranes were overloaded with cholesterol; microviscosity of cell membranes and membrane annular lipid regions was increased, cholesterol accumulation in the cells being in strong correlation with the incidence and duration of the trivial infections. In RA group only increased microviscosity of annular lipid regions was revealed. In the patient and relative groups the delayed engulfment and the slowed down time to reach the peak of reactive oxygen species generation after MP stimulation were revealed. Conclusion: We speculate that the abnormalities in monocyte – cholesterol interaction can exacerbate the insufficiency of antiinfectious defense and promote the aggravation of the infectious syndrome, which is known to be a risk factor of RA.