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

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Abstract
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.