Innate immune mechanisms in the pathogenesis of systemic lupus erythematosus (SLE)
Introduction
Innate immunity constitutes the primary host defense line against potential pathogens. Neutrophils and macrophages are the protagonic cells of the non-specific immune response [1]. To succeed with their physiological functions, e.g. chemotaxis, degranulation, generation of oxygen intermediates, phagocytosis and inflammatory reactions, activation is a sine qua non [2]. Leucocyte activators include bacterial products, complement fractions, immune complexes, chemokines, and cytokines among others [3]. Disturbances of innate immunity mechanisms may lead to a higher susceptibility to infections.
Non-specific immune response in systemic lupus erythematosus (SLE) has been neglected for several years now and the available information is scant and even, controversial [4], [5], [6], [7]. In SLE a common cause of complications are infectious diseases and susceptibility to them is consequence of the immune imbalance. Clearly, immunosuppressive therapy including glucocorticosteroids and cytotoxic drugs heighten this risk [8]. Furthermore, disease exacerbation often coincides with infection which represents a challenge for the differential diagnosis [9]. Immune dysequilibrium in SLE is represented by deficient cell-mediated as well as overexpressed humoral responses [10], [11]. This certainly, but not solely, contributes to the establishment of infectious processes. Leucocytes are primarily responsible for maintaining normal host defenses against invading microorganisms. These cells respond to infections by releasing several components from granules or lysosomes (neutrophils and monocytes, respectively) and by functional differentiation by enzymatic specialization. These enzymes may either remove tissue debris, or act intra- or extracellularly to kill and clear infectious agents [1].
The aim of this study was to explore several innate immune response mechanisms in SLE patients, namely polymorphonuclear cells (PMN) activation and chemotaxis as well as phagocytosis and intracellular enzyme activity in both PMN and monocytes in order to elucidate if indeed, alterations in these mechanisms constitute an inherent feature of the disease.
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Subjects
Sixty patients (57 females and three males) fulfilling at least four of the American College of Rheumatology criteria for SLE [12] were included in this study. None of them had inherited complement deficiency. Age ranged from 17 to 56 years (mean 33±10 years); disease duration was from 6 months to 21 years (mean 8±6 years). Patients with active or chronic infections, central nervous system involvement, renal failure, neutropenia or pregnancy were excluded. Subclinic infections were ruled out by
Intracellular enzyme activity in monocytes and PMN
The flow cytometric analysis of the intracellular activity of the enzymes tested did not show differences between patients and controls as far as cathepsin B and D and oxidative burst in PMN and monocytes are concerned. Notwithstanding, both enzymes showed a tendency to be diminished in SLE (Table 1). However, when patients were classified according to Mex-SLEDAI, those with active disease showed a significant diminished monocyte intracellular activity of cathepsin B and D when compared with
Discussion
Much is known about immune abnormalities in SLE where specific immune functions have been regarded with preference. Innate or non-specific immunity has been in certain sense left out of consideration, regretfully, for this response being the organism first line of defense. In this respect, it is worth to mention that infections are the main cause of morbidity and mortality in SLE patients [15], [16], [17].
Non-specific immunological abnormalities that facilitate infectious processes in SLE
Acknowledgements
This work was supported in part by research grants from the Consejo Nacional de Ciencia y Tecnologı́a (CONACYT 25606-M and 28408-M) Mexico City, Mexico. This work was the Ph.D. degree thesis of H. de la Fuente, Universidad Autónoma de San Luis Potosı́, School of Medicine, San Luis Potosı́, Mexico.
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