Elsevier

Immunology Letters

Volume 77, Issue 3, 2 July 2001, Pages 175-180
Immunology Letters

Innate immune mechanisms in the pathogenesis of systemic lupus erythematosus (SLE)

https://doi.org/10.1016/S0165-2478(01)00220-6Get rights and content

Abstract

Immune imbalance in SLE increases the susceptibility to infectious diseases. The aim of this study was to analyze several mechanisms related to non-specific immunity in this autoimmune disorder. We studied in vivo CD11b expression, phagocytosis, and chemotaxis in polymorphonuclear cells (PMN) from SLE patients. All tests were also performed under hrIL-8 stimulating conditions and analyzed by flow cytometry. Intracellular leucocyte (monocytes and PMN) enzyme activity was evaluated using specific substrates for cathepsin B and D, collagenase, and oxidative burst by flow cytoenzymology. An exaggerated in vivo CD11b expression was observed on PMN from SLE patients without noticeably in vitro effect upon hrIL-8. Similarly both, phagocytosis and chemotaxis were diminished and showed no response to hrIL-8 stimulation. The opposite was found in PMN from controls. Intracellular enzyme activity was comparable between groups as far as cathepsin B and D are concerned. A tendency of decreased oxidative-burst induction was noted in monocytes and PMN from SLE patients, whereas collagenase activity was found clearly increased in both leucocyte subpopulations. Our results may represent a deficient ability of the innate immune mechanisms for the clearance of infectious agents, immune complexes, satisfactory resolution of inflammatory processes and tissue repair in 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.

Section snippets

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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