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Interleukin-1 and Interleukin-6 Activities are Increased in the Cerebrospinal Fluid of Patients with CNS Lupus Erythematosus and Correlate with Local Late T-Cell Activation Markers
Jorge Alcocer-Varela
Department of Immunology and Rheumatology, Institute Nacional de la Nutrición Salvador Zubiran, México City, México
Deborah Aleman-Hoey
Department of Immunology and Rheumatology, Institute Nacional de la Nutrición Salvador Zubiran, México City, México
Donato Alarcon-Segovia
Department of Immunology and Rheumatology, Institute Nacional de la Nutrición Salvador Zubiran, México City, México
We examined cerebrospinal fluid (CSF) samples from 12 patients with SLE and active central nervous system (CNS) involvement for their levels of the following cytokines: interleukin- 1 (IL-1) by means of two different assays-the IL-1 responsive murine cell line LBRM 33-1a5 and an ELISA for IL-1 alpha; IL-2 by means of the CTLL cell line responsive to it; and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF) both determined by a specific ELISA. We found that SLE CSF had significantly higher levels of IL-1 and IL-6 than did those obtained at surgery from eight controls without inflammatory neurologic disease. IL-2 and TNF were not detectable in any of the CSF samples. We also studied the status of activation in CSF T cells using monoclonal antibodies against early (anti-IL-2R (CD25) and antitransferrin (CD71)), late (anti-T10) and very late (anti-VLA-1) activation antigens, and found increased percentages of T10-bearing (18 ± 2 vs 3 ± 0.7%) and VLA-1-bearing T cells (12 ± 2 vs 0.7 ± 0.2%) in SLE patients as compared to controls (both P < 0.01). Levels of IL-1 and IL-6 correlated with T10 and those of IL-1 correlated also with VLA-1. Markers of early T-cell activation did not differ in SLE and control CSF. Because of these findings we analysed the effect of recombinant IL,-I, IL-6 or normal CSF on normal T cells and found that they did not induce the expression of activation markers. However, incubation in SLE CSF caused CD25, T10 and VLA-1 activation markers to become significantly expressed on cultured normal T cells. This expression of T10 and VLA-1 was partially inhibited by pre-incubation in anti-human IL-1 alpha polyvalent antibody.
Our findings suggest increased in situ production of IL- and IL-6 and perhaps other factors in CNS lupus that might condition T-cell activation in the CNS compartment. These findings could have pathogenetic significance.
Key Words: Interleukin-1 • T-cell activation • CNS lupus erythematosus • CSF • cytokines • Interleukin-6 • Tumor necrosis factor
Lupus, Vol. 1, No. 2,
111-117 (1992)
DOI: 10.1177/096120339200100209
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