Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus.
OBJECTIVE
To evaluate the safety and clinical efficacy of administering an anti-interleukin-10 (anti-IL-10) monoclonal antibody (mAb) to systemic lupus erythematosus (SLE) patients with active and steroid-dependent disease. In addition, we sought to assess the effects of in vivo IL-10 neutralization on biologic markers of SLE.


METHODS
Treatment consisted of 20 mg/day intravenous administration of an anti-IL-10 murine mAb (B-N10) for 21 consecutive days, with a followup period of 6 months. Six patients were studied.


RESULTS
Treatment was safe and well tolerated. All patients developed antibodies against B-N10. Cutaneous lesions and joint symptoms improved in all patients beginning during B-N10 administration and continuing to month 6. The SLE Disease Activity Index decreased from a mean +/- SEM of 8.83+/-0.91 on day 1 to 3.67+/-0.67 on day 21 (P = 0.001), 1.50+/-0.84 at month 2, and 1.33+/-0.80 at month 6 (P<0.001). At the end of followup, the disease was clinically inactive in 5 of the 6 patients. Prednisone administration was decreased from a mean +/- SEM of 27.9+/-5.7 mg/day on day 1 to 9.6+/-2.0 mg/day at month 6 (P<0.005). Activity of immune and endothelial cells rapidly decreased, as assessed by the early evolution of several biologic markers.


CONCLUSIONS
This is the first report of IL-10 antagonist administration to humans. The study shows the involvement of IL-10 in the pathogenesis of SLE, and indicates that the use of IL-10 antagonists may be beneficial in the management of refractory SLE.
Llorente
L
L
Instituto Nacional de la Nutrición Salador Zubrinán, Mexico City, Mexico.
Richaud-Patin
Y
Y
García-Padilla
C
C
Claret
E
E
Jakez-Ocampo
J
J
Cardiel
M H
MH
Alcocer-Varela
J
J
Grangeot-Keros
L
L
Alarcón-Segovia
D
D
Wijdenes
J
J
Galanaud
P
P
Emilie
D
D
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D010865:Pilot Projects
D000911:Antibodies, Monoclonal; D016753:Interleukin-10