Interleukin 12 administration enhances Th1 activity but delays recovery from influenza A virus infection in mice
| Autor: | Dani S. Zander, S F Taylor, Wenn H Sun, Parker A. Small, Robert Cottey, Stefan Kostense, Bradley S. Bender, Stefan Harmeling |
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| Rok vydání: | 1998 |
| Předmět: |
Ratón
medicine.medical_treatment Antibodies Viral medicine.disease_cause Andrology Interferon-gamma Mice Immune system Orthomyxoviridae Infections Virology medicine Influenza A virus Animals Lung Inflammation Pharmacology Mice Inbred BALB C biology Tumor Necrosis Factor-alpha Interleukins Body Weight Th1 Cells Viral Load Interleukin-12 Recombinant Proteins Cytokine Immunoglobulin G Immunology biology.protein Interleukin 12 Female Tumor necrosis factor alpha Lymph Antibody T-Lymphocytes Cytotoxic |
| Zdroj: | Antiviral Research. 38:117-130 |
| ISSN: | 0166-3542 |
| Popis: | Interleukin 12 (IL-12) directs the differentiation of undifferentiated T helper (Th0) cells to T helper type 1 (Th1) cells and induces a cell-mediated immune response. To evaluate the effect of IL-12 on the course of influenza A virus infection, BALB/c mice were administered a daily intraperitoneal dose of 1000 ng of IL-12 or saline on days -1 to +4 for a total of six treatments. The treatment generally enhanced Th1-mediated responses. IFNgamma lung concentrations were 1193 +/- 275 pg/100 microl in controls and 3693 +/- 745 pg/100 microl in IL-12-treated mice at day 5. IFNgamma levels were undetectable at day 13 in controls and 1335 +/- 220 pg/100 microl in IL-12-treated mice. Cytokine production was also assessed at the single-cell level for mediastinal lymph nodes. IL-12 treatment increased the number of IL-2- and IFNgamma-producing cells and decreased the number of IL-4- and IL-10-producing cells. IL-12 treatment decreased the anti-influenza antibody response, especially anti-influenza IgG1 antibody resulting in an increased IgG2a/IgG1 ratio. Primary pulmonary CTL activity on day 5 was low for both groups (10% specific lysis). Secondary CTL activity at day 11 was higher for control mice than for IL-12-treated mice on day 11 (44 versus 34%), but not on day 13. Despite this overall enhancement of Th1-mediated immune functions, the IL-12 treatment increased severity of the disease. Following infection, control and IL-12-treated mice decreased their body weight to approximately 75% of their initial weight. After day 5, the control mice started to recover, while IL-12-treated mice did not begin recovering until day 9. Pulmonary viral titers were 1.6 +/- 0.3 TCID50 in controls at day 5 compared to 2.4 +/- 0.3 for IL-12-treated mice (P0.01). In addition, control mice had significantly less severe inflammation and damage on histologic examination. Serum TNFalpha concentrations, undetectable in control mice, were elevated by IL-12 treatment up to 80 pg/ml at day 5 and decreased to zero at day 13. It is concluded that IL-12 administration to influenza-infected mice induces a switch from a Th2- to a Th1-mediated response, but inhibits recovery probably through induction of TNFalpha. |
| Databáze: | OpenAIRE |
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