Article Figures & Data
Figures
- Fig. 1.
Plasma concentrations of IFN-γ, IL-10, TNF-α, IL-8, IL-6, IL-4, and IL-12 after the first s.c. injection of IL-12. Median plasma concentrations of IFN-γ, IL-10, TNF-α, IL-8, IL-6, and IL-4 were assessed immediately before and during 7 days after the first s.c. injection of 0.1 μg/kg rHuIL-12 (♦, 3 patients), 0.5 μg/kg (○, 19 patients), or 1 μg/kg (▴, 4 patients). Dotted lines, top limit of the normal range.
- Fig. 2.
Cytokine concentrations after the first injection of IL-12 (A), compared with concentrations after the seventh injection at the same (B) or escalated dose of IL-12 (C). Median plasma concentrations of IL-10 (top panels), TNF-α (middle panels), and IFN-γ (bottom panels) were assessed immediately before and during 7 days after the first and seventh injections of rHuIL-12. The first injection of 0.5 μg/kg was given to 13 patients (A, D, and G). Seven of these patients received subsequent injections at the same dose level (B, E, and H), and the remaining 6 patients received subsequent injections at the 1 or 1.25 μg/kg dose levels (C, F, and I). Significant differences (P < 0.05) between cytokine concentrations before and after each IL-12 injection are indicated by asterisks. Dotted lines, top limit of the normal range.
- Fig. 3.
Lymphocyte subsets after repeated injections of rHuIL-12. Absolute numbers of NK cells (CD3−, 16+, and/or 56+), B cells (CD19+), T-helper cells (CD3+ and 4+), and cytotoxic T cells (CD3+ and 8+) were assessed immediately before and during 26 days after the first rHuIL-12 injection of 0.5 μg/kg in 9 patients. Subsequent injections were at the 0.5 μg/kg (n = 4), 1 μg/kg (n = 3), or 1.25 μg/kg (n = 2) dose levels. Arrows, rHuIL-12 injections. For each time point, the median result of the 9 patients is depicted as a diamond, and the interquartile range is depicted with horizontal dashes. Dotted lines, bottom and (for CD3+ and 8+ T cells only) top limits of the normal range as assessed in 61 healthy controls. Significant differences (P < 0.05) between baseline lymphocyte subset counts and the respective counts during or after rHuIL-12 treatment are indicated by asterisks.
Tables
- Table 1
Baseline and peak cytokine concentrations after the first s.c. administration of rHuIL-12
0.1 μg/kg (n = 3) 0.5 μg/kg (n = 19) 1 μg/kg (n = 4) Baseline Peak Baseline Peak Baseline Peak Median Range Median Range Median Range Median Range Median Range Median Range IL-12 (pg/ml) <50 <50 <50a 298g 116–830 <50 548 475–2630 IFN-γ (IU/ml) <0.03 <0.03–0.4 2.6h 1.4–2.9 <0.03 <0.03–1.4 13g 1.5–41 0.4 <0.03–0.5 55 12–184 IL-10 (pg/ml) <1b 15 <1c <1–6 22g 4–49 <1 37h 27–81 TNF-α (pg/ml) 26 21–40 84h 73–108 25 8–83 95g 60–143 25 7–33 168h 149–223 IL-8 (pg/ml) 5 <1–15 24 11–53 11d <1–35 38h 14–223 <1 <1–8 53h 32–87 IL-6 (pg/ml) 6e <2–10 25 22–27 16f <2–79 82g 17–280 <2 83h 42–137 -
As described in “Results,” induction of the various cytokines did not occur in all patients. Only data from patients with increments of cytokine concentrations post-IL-12 in comparison with baseline are shown. Symbols denote numbers of patients in which increments of cytokine concentrations have been observed.
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a n = 10.
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b n = 1.
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c n = 13.
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d n = 14.
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e n = 2.
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f n = 16.
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g P < 0.001; paired comparison between peak and baseline levels.
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h P < 0.05.
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- Table 2
Leucocyte subsets after the first s.c. injection of rHuIL-12
0.1 μg/kg (n = 3) 0.5 μg/kg (n = 15) 1 μg/kg (n = 4) Baseline cell counta Nadira Baseline cell counta Nadira Baseline cell counta Nadira Median Range Median Range Median Range Median Range Median Range Median Range Lymphocytes 1.8 1.5–1.9 0.8b 0.5–0.8 1.3 0.5–2.9 0.5b 0.1–1.1 1.4 1.0–2.3 0.3c 0.2–0.5 Neutrophils 4.0 3.5–4.1 0.9 4.2 2.7–6.8 1.5b 0.7–4.7 3.7 2.9–5.3 1.4c 1.1–1.7 Monocytes 0.53 0.46–0.66 0.21 0.17–0.38 0.30 0.17–0.58 0.15b 0.03–0.43 0.35 0.29–0.5 0.11c 0.02–0.16 -
a Absolute numbers are expressed as (number of cells × 109/liter).
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b P < 0.001; paired comparisons between nadirs and baseline counts.
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c P < 0.05.
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Volume 9, Issue 1
