Table 2.
Treatment | Administration of treatment in relation to the time of infection | Main effect in infected mice |
Brucella CFU in the spleena |
References | |
---|---|---|---|---|---|
Acute before 14 days | Chronic after 15 days | ||||
Rabbit anti-Brucella |
2 h, 16 h before or 2 h after |
Immune serum from Brucella infected mice directed against a variety of different antigens |
↓ |
↓ |
[106] |
Murine anti-Brucella |
2 h, 16 h before or 2 h after |
Immune serum from Brucella infected mice directed against a variety of different antigens |
↓ |
↓ |
[84,98,107] |
Anti-LPS |
16 h before |
Immune murine sera against Brucella LPS |
↓ |
↓ |
[84] |
Anti-O:9 |
16 h before |
Immune murine sera against Yersinia enterocolitica O:9. It protects mice but to a lesser extent than anti-Brucella |
↓ |
↓ |
[84] |
Anti-peptido-glycan |
16 h before |
Polyclonal immune sera against peptidoglycan protein complex, probably contaminated with LPS |
↓ |
↓ |
[84] |
Mabs anti-O- chain LPS |
4 h before |
Several antibody isotypes reacting against A, M and C epitopes of the B. abortus O chain of LPS |
↓ |
↓ |
[35,108-110] |
Mabs anti-Omps |
24 h before |
Against Omps of molecular weight 10, 16.5, 19, 25–27, 31–34, 36–38 and 89 |
↔ |
↔ |
[109] |
Mab-anti-Omp16 |
24 h before |
It induces lower protection than anti- O chain antibodies; IgG2a isotype |
↓ |
ND |
[109] |
Mab-anti-Omp25 |
24 h before |
It induces lower protection than anti-O chain antibodies; IgG2a isotype |
↓ |
ND |
[109] |
Mab-anti-Omp2b |
4 h before |
Reacts against B. abortus Omp2b, which generally is not accessible in smooth bacteria |
↔ |
ND |
[35] |
Mab-anti-Omp31 |
24 h before |
It induces lower protection than anti-O chain LPS antibodies; IgG2a isotype |
↓ |
ND |
[109] |
Spleen cells |
Same day as infection |
Protection was efficiently transferred to naive mice using spleen cells from mice infected 5 or 12 weeks earlier |
ND |
↓ |
[111] |
Immune Tcells |
2 h after infection |
It gave similar protection than CD8+ or CD4+ cells passively transferred. Immune cells from six week infected mice. Before 4 week there is no protection. |
↓ |
ND |
[98,112] |
Immune CD4+T cells |
2 h after infection |
It gave similar protection than CD8+ cells passively transferred. Immune cells from six week infected mice. Before 4 week there is no protection |
↓ |
ND |
[107] |
Immune CD8+T cells |
2 h after infection |
It gave similar protection than CD4+ cells passively transferred. Immune cells from six week infected mice. Before 4 week there is no protection |
↓ |
ND |
[107] |
Serum anti-Brucella and T cells |
2 h after infection |
Enhanced protection over administration of just T cells or Abs alone |
↓ |
ND |
[107] |
Immune T cell+anti- INF-γ |
Anti- INF-γ 1day before T cells with challenge |
It gave similar protection than passively transferred T cells |
↔ |
ND |
[112] |
Bovine Mø |
1 day before infection |
Transferred to NK1.1 cell-depleted Rag-1−/− mice |
↔ |
ND |
[60] |
Bovine Mø+γδT cells |
1 day before infection |
Transferred to NK1.1 cell-depleted Rag-1−/− mice |
↓ |
ND |
[60] |
Bovine Mø+CD4 T cells |
1 day before infection |
Transferred to NK1.1 cell-depleted Rag-1−/− mice |
↔ |
ND |
[60] |
INF-γ |
1 day before and 2 and 4 day after |
It Induces splenomegaly. Mice show enhanced peritoneal and splenic macrophage bactericidal activity |
↓ |
ND |
[113] |
IL-12 |
With the infection and every 3 days after |
The levels of INF-γ increase during the third week of infection |
↔ |
↓ |
[114] |
IL-1α |
4 h before |
CSF-1 increases in serum during the first 12 h. Colony forming cells increase in the spleen, mainly Mø and PMNs. Thirty days after treatment, the effect is terminated. |
↓ |
↓ |
[28] |
Transfer factor |
At the sametime |
No effect in immune enhancement or antibody response |
ND |
↔ |
[115] |
Indomethacin |
Daily s. c. for 7 days |
Decrease of the cyclooxygenase activity by 80 to 90 % in spleen. Reduction of PGE2 |
↓ |
ND |
[113] |
Poly A:U |
2 h before and 2, 4, and 6 days after |
Activation of NK cell activity |
↔ |
ND |
[116] |
Poly A:U |
At the sametime |
Polyadenylic acid-polyuridylic acid (poly A: U) is a non-toxic adjuvant that potentiates both humoral and cell-mediated immune responses |
↓ |
↓ |
[27,117] |
Cyclosporine |
Daily for 4 weeks |
It induces low inflammatory response in spleen and liver. No significant changes in spleen macrophage population |
ND |
↑ |
[107] |
Corticosteroids |
24 h before |
It has a broad anti-inflammatory effects |
↑ |
↑ |
[3] |
Anti-Ia |
24 h before |
It depletes mostly B cells and some T cell subpopulation with “suppressor” activity |
ND |
↔ |
[111] |
Anti-CD8+ T cells |
5 days before and 3 per week |
Depletion of CD8+ cells. DTH response was unaffected after treatment. Treatment abolished the IgG antibody response without affecting bacterial numbers. |
ND |
↑ |
[111] |
Anti-CD8+ T cells |
1 day before and every 4 days after |
Depletion of CD8+ cells, significant increase of Møs in spleen. No significant effect in the number of CD4+, NK or γδ T cells |
ND |
↑ |
[118] |
Anti-CD8+ |
1 day before and every 3 days after |
Depletion of CD8+ lymphocytes involved in cell mediated cytotoxicity of infected cells |
ND |
↔ |
[119] |
Anti-CD8+ |
2 days before and 1,4,7 10 days after |
Depletion of CD8+ lymphocytes involved in cell mediated cytotoxicity of infected cells |
ND |
↑ |
[56] |
Anti-CD4+ |
2 days before and 1,4,7 10 days after |
Influences the Th1 profile mainly INF-γ. It induces basal levels of IL2 and IL4 |
ND |
↓ |
[56] |
Anti-CD4+ |
|
Reduces granulomatous inflammation, which seems to be mediated mainly by CD4+ T cells |
ND |
↔ |
[119] |
Anti-CD25+ T cells |
3 days before |
Depletion of CD4+ regulatory T cells. Increase levels of INF-γ in spleen cells |
ND |
↓ |
[120] |
Anti-NK1.1cells |
24 h before |
Depletion of NK cells and activity |
↔ |
ND |
[116] |
Anti-asialo-GM1 |
24 h before and 3 day after |
Depletion of NK cells and activity |
↔ |
ND |
[116] |
Anti-PMN-RB6 |
24 h before and3, 6, 9 days after |
It depletes neutrophils and a small population of Møs. It does not affect the course of brucellosis. In some cases CFU decrease in numbers after 9 days of treatment |
↔/↓ |
ND |
[48],unpublished results] |
Anti-IL-10 |
1 day before and 4 days after |
The levels of INF-γ increase during the first week of infection |
↓ |
ND |
[121] |
Anti-IL-10 |
1 day before and 4 days after |
Augments the production of INF-γ in spleen cells of both, sensitive and resistant mouse strains |
↓ |
ND |
[122] |
Anti-IL-12 |
4 h before, or 2 days after, or 7 days after |
Decrease in spleen weight and spleen inflammation in relation to infected non-treated mice. There is granuloma reduction and low levels of INF-γ |
↑ |
↑ |
[123,124] |
Anti-IL-4 |
24 h before and 4 days after |
Removal of IL-4 It depresses the Th2 Ab response and indirectly may favor the Th1 response |
↓ |
ND |
[122] |
Anti-INF-γ |
1 day before infection |
Reduces splenomegaly |
↑ |
ND |
[112] |
Anti-INF-γ |
1 day before and every 5 days after |
No significant effect was observed even after administration with IL-12 |
ND |
↔ |
[114] |
Anti-INF-γ |
1 day before and 4 days after |
It removes secreted INF-γ and depressed Th1 response |
↑ |
ND |
[121] |
Anti-INF-γ |
24 h before and 4 days after |
It removes secreted INF-γ and depressed Th1 response |
↑ |
ND |
[122] |
Anti-TNF-α |
1 day before and every 4 days after |
No significant effect in the number of PMNs, CD4, CD8, NK, γδ T cells or Møs is observed |
ND |
↑ |
[118] |
Anti-TNF-α |
4 h before, or 2 days after, or 7 days after |
Decrease in spleen weight and spleen inflammation with respect to the infected non-treated mice. INF-γ is detected at normal levels |
↑ |
↔ |
[60,63,124] |
Anti-TCRγδ | The same day and 3 days after | Removes Tγδ cells if innate immunity. Depletion has similar effect in IL/17Rα KO, INF-γ KO and GM-CSF KO mice | ↑ | ND | [60] |
a (↑) Significantly higher numbers of CFU in spleen than in controls; (↓) significantly lower numbers of CFU in spleen than in controls; (↔) No significant number of CFU in spleen in relation to the controls; ND, not done.