Inhibition of Interleukin-10 as a Therapeutic Strategy in Systemic Lupus Erythematosus

[Guest guest]

Inhibition of Interleukin-10 as a Therapeutic Strategy in Systemic Lupus

Erythematosus

S. Fauci

[Copyright © 1998, 1999, 2000 by The McGraw-Hill Companies, Inc. Reproduced with

permission of The McGraw-Hill Companies.]

--------------------------------------------------------------------------------

Several lines of evidence suggest an important role for interleukin (IL)-10 in

the pathogenesis of systemic lupus erythematosus (SLE). Patients with SLE

overproduce IL-10 and serum IL-10 levels correlate with disease severity. SCID

mice infused with blood cells from patients with SLE produce

anti-double-stranded DNA antibodies; production of these antibodies, which are

characteristic of SLE, is unaltered by treatment of the mice with anti-IL-6, but

is almost completely abolished by anti-IL-10 treatment. IL-10 generally inhibits

proinflammatory cytokine production by mononuclear cells and also impairs T cell

activation; these properties are consistent with the observed impairment of

cell-mediated immunity that is often observed in patients with SLE.

Llorente and colleagues (2000), conducted a pilot study to determine the effect

of anti-IL-10 therapy on the clinical course of SLE. The study subjects included

six patients with glucocorticoid-dependent SLE; a murine monoclonal anti-IL-10

antibody that neutralizes human IL-10 was administered intravenously at a dose

of 20 mg/day for 21 days. Therapy was halted in one patient who developed chills

during antibody infusion on day 16; no serious adverse events were attributed to

the treatment. The ratio of anti-IL-10 to IL-10 in the plasma exceeded 5000:1 in

all patients when measured in the day 9-11 window. Disease activity index scores

declined significantly in all patients during treatment; interestingly, scores

continued to decline at day 60 and remained stable through 6 months of

follow-up. The average daily prednisone dose decreased significantly, from

approximately 28 mg daily at baseline to 24 mg daily at 1 month, 21 mg daily at

2 months, and 10 mg daily at 6 months. In addition, partial restoration of T

cell function occurred in vitro.

These findings support further studies on the use of IL-10 antagonists in the

treatment of SLE and other autoimmune diseases.

--------------------------------------------------------------------------------

Reference

1.. Llorente L et al: Clinical and biologic effects of anti-interleukin-10

monoclonal antibody administration in systemic lupus erythematosus. Arthritis

Rheum 43:1790, 2000 [PMID 10943869]