Table 2.
Serum and tissue cytokine and chemokine levels and effects of cidofovir treatment on infections initiated by 5-μl and 50-μl i.n. inoculation volumes of the same infectious dose of a syncytium-forming cowpox virus.
| 5-μl Infection
|
50-μl Infection
|
|||||
|---|---|---|---|---|---|---|
| Factora | Uninfected | Cidofovir | Placebo | Cidofovir | Placebo | |
| GM-CSF | serum | <0.1 ± 0.0 | 0.5 ± 0.5* | 3.7 ± 2.4ΨΨΨ (>37) b | 1.0 ± 0.9** | 8.7 ± 8.5ΨΨΨ (>87) |
| lungs | 3.0 ± 2.5 | 9.8 ± 1.2** | 15 ± 3.0φφ, ΨΨΨ | 17 ± 1.6** | 22 ± 3.5ΨΨΨ | |
| snout | 3.8 ± 2.2 | 12 ± 7.7 | 14 ± 9.2Ψ | 13 ± 8.1 | 11 ± 6.8Ψ | |
| IFNγ | serum | 9.8 ± 8.5 | <1 ± 0.0* | 16 ± 29 | <1 ± 0.0* | 65 ± 130 |
| lungs | 95 ± 48 | 65 ± 18 | 69 ± 31φφφ | 645 ± 97*** | 349 ±109ΨΨΨ | |
| snout | 42 ± 26 | 3,006 ± 1,042 | 2,679 ± 891ΨΨΨ (64) | 2,229 ± 939 | 2,044 ± 825ΨΨΨ (49) | |
| IL-1β | serum | <1 ± 0.0 | 7.8 ± 2.2** | 21 ± 8.7ΨΨΨ (>210) | 10 ± 3.7** | 19 ± 5.0ΨΨΨ (>190) |
| lungs | 7.1 ± 8.4 | 34 ± 4.8 | 38 ± 8.6φΨ | 51 ± 13 | 68 ± 31Ψ | |
| snout | 19.6 ± 8.0 | 1,233 ± 2,146Ψ | 2,573 ± 2,550ΨΨ (131) | 577 ± 356 | 1,092 ± 1,228 (56) | |
| IL-2 | serum | 0.3 ± 0.5 | 1.0 ± 0.4* | 9.4 ± 7.0ΨΨ (31) | 2.7 ± 1.4** | 6.9 ± 2.0ΨΨΨ (23) |
| lungs | 0.1 ± 0.2 | 3.3 ± 0.4*** | 5.9 ± 1.1φφφ,ΨΨΨ (59) | 15 ± 3.8 | 16 ± 3.7ΨΨΨ (16) | |
| snout | 0.1 ± 0.2 | 4.4 ± 2.0 | 5.0 ± 2.6ΨΨ (50) | 4.2 ± 1.6 | 3.9 ± 1.7ΨΨΨ (39) | |
| IL-3 | serum | <0.1 ± 0.0 | <0.1 ± 0.0* | 2.6 ± 2.1ΨΨΨ (>26) | 0.5 ± 1.0* | 8.1 ± 11ΨΨΨ (>81) |
| lungs | 6.0 ± 4.0 | 5.4 ± 0.7** | 8.8 ± 1.8φφφ | 18 ± 4.5*** | 43 ± 12ΨΨΨ | |
| snout | 4.1 ± 1.4 | 19 ± 17 | 26 ± 20Ψ | 15 ± 8.8 | 16 ± 9.3Ψ | |
| IL-5 | serum | 0.5 ± 0.8 | 1.9 ± 0.5*** | 22 ± 9.8ΨΨΨ (44) | 4.0 ± 1.1* | 15 ± 9.1ΨΨ (30) |
| lungs | 0.8 ± 1.3 | 7.8 ± 1.4** | 14 ± 4.3φ,ΨΨΨ (18) | 33 ± 9.9 | 37 ± 19ΨΨΨ (46) | |
| snout | 2.3 ± 2.2 | 2.7 ± 4.7 | 5.4 ± 5.7 | 1.5 ± 1.0 | 2.5 ± 2.8 | |
| IL-6 | serum | 39 ± 61 | 70 ± 54* | 2,102 ± 1,800Ψ (54) | 254 ± 222** | 2,781 ± 1,583ΨΨ (71) |
| lungs | 2.5 ± 1.3 | 20 ± 27 | 51 ± 31φφφ (20) | 12,667 ± 4,537*** | 44,886 ± 5,208ΨΨΨ (17,954) | |
| snout | 7.8 ± 4.1 | 18,723 ± 7,733***, ΨΨΨ | 51,330 ± 2,523φ, ΨΨΨ (6,580) | 2,449 ± 3,558*** | 36,770 ± 15,570ΨΨΨ (4,714) | |
| IL-9 | serum | <1 ± 0 | 201 ± 91*** | 760 ± 170ΨΨΨ (>760) | 356 ± 336 | 664 ± 127ΨΨΨ (>664) |
| lungs | <1 ± 0 | 550 ± 160*** | 1,022 ± 113φφ, ΨΨΨ (>1,022) | 867 ± 218** | 1,280 ± 109ΨΨΨ (>1,280) | |
| snout | <1 ± 0 | 1,106 ± 271 | 1,246 ± 415ΨΨΨ (6,580) | 907 ± 166 | 1,016 ± 260ΨΨΨ (>1,016) | |
| IL-10 | serum | 17 ± 11 | 1.6 ± 2.7** | 96 ± 60φφΨ | 18 ± 22** | 1833 ± 991ΨΨ (108) |
| lungs | 23 ± 3.0 | 14 ± 5.7** | 42 ± 22φφφ, ΨΨ | 164 ± 78*** | 1,726 ± 715ΨΨΨ (75) | |
| snout | 15 ± 12 | 810 ± 562 | 1,093 ± 911Ψ (73) | 444 ± 120 | 732 ± 469ΨΨ (49) | |
| MCP-1 | serum | 314 ± 222 | 332 ± 57*** | 1,382 ± 306ΨΨΨ | 589 ± 248** | 1,429 ± 401ΨΨΨ |
| lungs | 120 ± 56 | 437 ± 16 | 450 ± 65φφ φ, ΨΨΨ | 1,472 ± 205 | 1,709 ± 345ΨΨΨ (14) | |
| snout | 243 ± 48 | 379 ± 361 | 618 ± 256ΨΨ | 488 ± 133 | 529 ± 197ΨΨ | |
| TNFα | serum | 2.7 ± 4.7 | 6.3 ± 6.0 | 12 ± 11 | 6.4 ± 4.9* | 28 ± 17ΨΨ (10) |
| lungs | 8.4 ± 5.2 | 21 ± 12 | 34 ± 20Ψ | 30 ± 11*** | 48 ±17ΨΨΨ | |
| snout | 19 ± 5 | 70 ± 86 | 143 ± 10Ψ | 95 ± 41* | 176 ± 75ΨΨΨ | |
Determined on day 7 of the 50-μl volume infection and on day 9 for the 5-μl volume infection, which was near the death of each group. Cidofovir was given once a day for 2 days starting 24 h after virus exposure. Levels are in pg/ml ± SD (N=6).
Values in parentheses are fold differences of placebos from untreated mice. Only placebos with fold increases ≥10 are shown.
P<0.05,
P<0.01,
P< 0.001, comparing effects of cidofovir treatment to the respective placebo control.
P<0.05,
P<0.01,
P<0.001, comparing 5-μl placebo to 50-μl placebo.
P<0.05,
P<0.01,
P<0.001, comparing 5-μl and 50-μl placebo groups to uninfected animals.