Neutrophils and Th1 cells are required for the therapeutic efficacy of thymosin α 1
Group . | Mice* . | Treatment† . | Neutrophils/lung, × 103‡ . | Chitin content‡ . | MST, d‡ . |
|---|---|---|---|---|---|
| 1 | BMT | None | 71 ± 8 | 44 ± 6 | 4.5 |
| 2 | BMT | G-CSF | 544 ± 28§ | 25 ± 4§ | 10§ |
| 3 | BALB/c | None | 54 ± 4 | 38 ± 4 | 5.5 |
| 4 | BALB/c | Thymosin α 1 | 714 ± 12§ | 18 ± 2 | > 60§ |
| 5 | NOD/SCID | None | 194 ± 19 | 68 ± 12 | 6 |
| 6 | NOD/SCID | Thymosin α 1 | 491 ± 22§ | 31 ± 7§ | 15§ |
| 7 | NOD/SCID | Thymosin α 1 + neutrophil depletion | 69 ± 14§ | 59 ± 10 | 5.5 |
| 8 | IFN-γ deficient | None | 84 ± 10 | 49 ± 5 | 7.5 |
| 9 | IFN-γ deficient | Thymosin α 1 | 681 ± 44§ | 25 ± 4§ | 18§ |
| 10 | IL-4 deficient | None | 88 ± 8 | 32 ± 5 | 22 |
| 11 | IL-4 deficient | Thymosin α 1 | 704 ± 51§ | 0.9 ± 0.3§ | > 60§ |
Group . | Mice* . | Treatment† . | Neutrophils/lung, × 103‡ . | Chitin content‡ . | MST, d‡ . |
|---|---|---|---|---|---|
| 1 | BMT | None | 71 ± 8 | 44 ± 6 | 4.5 |
| 2 | BMT | G-CSF | 544 ± 28§ | 25 ± 4§ | 10§ |
| 3 | BALB/c | None | 54 ± 4 | 38 ± 4 | 5.5 |
| 4 | BALB/c | Thymosin α 1 | 714 ± 12§ | 18 ± 2 | > 60§ |
| 5 | NOD/SCID | None | 194 ± 19 | 68 ± 12 | 6 |
| 6 | NOD/SCID | Thymosin α 1 | 491 ± 22§ | 31 ± 7§ | 15§ |
| 7 | NOD/SCID | Thymosin α 1 + neutrophil depletion | 69 ± 14§ | 59 ± 10 | 5.5 |
| 8 | IFN-γ deficient | None | 84 ± 10 | 49 ± 5 | 7.5 |
| 9 | IFN-γ deficient | Thymosin α 1 | 681 ± 44§ | 25 ± 4§ | 18§ |
| 10 | IL-4 deficient | None | 88 ± 8 | 32 ± 5 | 22 |
| 11 | IL-4 deficient | Thymosin α 1 | 704 ± 51§ | 0.9 ± 0.3§ | > 60§ |
Mice that received BM transplants (groups 1 and 2) or treated with cyclophosphamide (groups 3-11) were infected with 2 × 107Aspergillus conidia intranasally for 3 consecutive days.
In mice that received BM transplants, G-CSF (250 μg/kg intravenously) was given daily, beginning the day of the BM infusion, in concomitance with the infection and continuing for an additional 3 days. In cyclophosphamide-treated mice, thymosin α 1 (400 μg/kg intraperitoneal) was given for 5 consecutive days, beginning the day of the infection; neutrophil depletion was obtained by treatment with 1 mg RB6-8C5 antibody intravenously a day before and after the infection.
Lungs were assessed for the presence of fungal cells (chitin content, expressed as microgram glucosamine per lung) and neutrophils (FACS analysis) a day (untreated mice, None) or 3 days (treated mice) after the last Aspergillus inoculation. Values are the mean ± SE for the neutrophil and chitin columns. MST indicates median survival time.
P < .05, treated versus untreated mice. Each type of intact mice survived the infection and efficiently controlled the fungal growth.