Administration of Neutralizing Antibodies to Interleukin-6 (IL-6) Reduces Experimental Autoimmune Encephalomyelitis and Is Associated with Elevated Levels of IL-6 Bioactivity in Central Nervous System and Circulation

Table 1 Effect of antibodies to IL-6 on the disease course of actively induced EAE

Experimental Group	Antibody Dose	Time of Antibody Administration (days relative to EAE induction)	Disease Incidence	Mortality	Mean Maximal Disease Score (±SEM)	Mean Cumulative Disease Score^a
Experimental Group	Antibody Dose		Disease Incidence	Mortality	Mean Maximal Disease Score (±SEM)	Absolute (±SEM)	%
Experiment 1
PBS	—	−1, 7	7/10	3/10	2.4 ± 0.67	48.8 ± 21.4	100
Anti-β-gal.	2 mg	−1, 7	5/8 (10)^b	1/8	1.8 ± 0.62	24.8 ± 18.3	51
Anti-IFNγ	2 mg	−1, 7	9/10	6/10	3.7 ± 0.58	80.7 ± 21.1	165
Anti-IL-6	2 mg	−1, 7	2/9 (10)^c	0/9	0.6 ± 0.38^d	2.6 ± 1.8^d	5
Experiment 2
PBS	—	−1, 7	7/10	1/10	1.9 ± 0.50	29.2 ± 11.3	100
Anti-β-gal.	2 mg	−1, 7	0/2 (10)	0/2	—	—	—
	1 mg	−1, 7	4/5	0/5	1.6 ± 0.40	15.8 ± 7.2	54
	0.5 mg	−1, 7	4/5	1/5	2.2 ± 0.80	42.4 ± 30	145
Rat IgG	2 mg	−1, 7	5/8 (10)	0/8	1.4 ± 0.42	18.4 ± 6.8	63
	1 mg	−1, 7	3/5	1/5	1.4 ± 0.60	23.2 ± 17.2	80
	0.5 mg	−1, 7	2/5	0/5	1.3 ± 0.75	14.0 ± 19.8	48
Anti-IL-6	2 mg	−1, 7	2/10^c	0/10	0.5 ± 0.34^d	4.2 ± 3.7^d	14
	1 mg	−1, 7	1/5	0/5	0.4 ± 0.40	6.8 ± 7.6	23
	0.5 mg	−1, 7	1/5	0/5	0.4 ± 0.40	3.6 ± 8.0	12
Experiment 3
PBS			5/10	1/10	1.3 ± 0.54	24.3 ± 16.1	100
Anti-β-gal.	0.5 mg	−1, 7	5/7 (8)	1/7	1.9 ± 0.63	29.1 ± 18.3	120
	0.5 mg	−1	4/7	4/7	2.9 ± 1.01	79.3 ± 30.4	326
	0.5 mg	7	6/9	1/9	1.7 ± 0.53	27.3 ± 15.2	112
Rat IgG	0.5 mg	−1, 7	1/2 (10)	0/2	—	—	—
	0.5 mg	−1	4/10	1/10	1.1 ± 0.55	15.8 ± 12.3	65
	0.5 mg	7	7/10	1/10	1.8 ± 0.49	25.4 ± 12.1	105
Anti-IL-6	0.5 mg	−1, 7	1/9 (10)	0/9	0.2 ± 0.20	3.1 ± 3.3	12
	0.5 mg	−1	2/10	0/10	0.4 ± 0.27	4.7 ± 3.5	19
	0.5 mg	7	6/9	1/9	2.0 ± 0.58	27.6 ± 12.6	114

EAE was actively induced by immunizing SJL mice s.c. with MSCH in CFA and by giving pertussis toxin i.v. Different doses of the mAb, purified rat IgG, or the same volume of PBS were given i.p. as indicated. Animals were scored daily as described in Materials and Methods.
^aThe mean cumulative disease score was calculated by adding the mean daily disease scores from all the animals in a group over the observation period (30 days) (expressed as the absolute value ± SEM and as the percentage of the score of the PBS group). Scores for each group are compared with the scores for the PBS group in that experiment.
^bThe number of animals in each group at the start of the experiment is indicated in the parentheses; only animals that survived the second Ab dose (on Day 7) were taken into account for calculations.
^cp < 0.05, one-tailed Fisher exact test.
^dp < 0.05, Mann-Whitney U test.

ISSN: 1528-3658