Summary auto-generated
This research article investigates immune responses to Pseudomonas aeruginosa infection using mouse models. The study examined how IL-12 and IL-10 cytokines influence survival outcomes and immune function during P. aeruginosa lung infection. Researchers used various mouse strains and knockout models to assess the roles of interferon-gamma (IFN-γ) and other immune markers. The experiments measured survival rates, bacterial burden, and cytokine production over a 20-day infection period. Results demonstrated that IL-12-mediated responses promoted protective immunity, while IL-10 had suppressive effects. Treatment with recombinant IL-12 (rIL-12) enhanced survival and increased IFN-γ production in infected mice. The study also evaluated immune responses in mice lacking specific cytokine signaling pathways. Data showed correlations between early cytokine responses and disease progression. These findings suggest that modulating IL-12 and IL-10 balance could be therapeutically relevant for P. aeruginosa infections, indicating potential targets for immune-based interventions in bacterial pneumonia.
Key findings
- IL-12 treatment enhanced survival in P. aeruginosa-infected mice by promoting IFN-γ production and controlling bacterial burden
- IL-10 suppressed protective immune responses and worsened outcomes during P. aeruginosa infection
- The balance between IL-12 and IL-10 cytokines critically determines immune control of P. aeruginosa lung infection
- Early cytokine responses (IFN-γ levels) correlated with survival outcomes and bacterial clearance
- Cytokine-based immunotherapy targeting IL-12 enhancement may improve outcomes in P. aeruginosa respiratory infections
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Abstract
Interleukin-12 (IL-12) is thought to play an important role as a modulator of levels of IL-10 and interferon-γ (IFN-γ). To address the therapeutic effects of rIL-12 in an endogenous sepsis model in mice, which closely mimics the pathophysiology of septicaemia in man, the effects of rIL-12 on the levels of cytokines such as IL-10 and IFN-γ, and on the survival of septic mice infected with Pseudomonas aeruginosa PAO1 were examined. First, in the endogenous sepsis model, the serum levels of IFN-γ and IL-10 remained normal until days 8 and 10, respectively, when significant rises were seen. On day 11, levels of IFN-γ returned to normal, but levels of IL-10 remained high. Interestingly, the IL-10 serum level reached a maximum 2 days later than the IFN-γ serum level. In the light of these results, septic mice were given 0.01 µg of rIL-12 by intraperitoneal injection and the serum levels of endogenous cytokines and the survival times were examined. Mice treated with rIL-12 on days 5, 6 and 7 after infection survived significantly longer than control septic mice treated with saline only. Treatment with rIL-12 also led to a significant increase of the serum IFN-γ level and a decrease of the serum IL-10 level on day 11. These results suggest that rIL-12 exerts therapeutic activity against endogenous sepsis caused by P. aeruginosa by stimulating pro-inflammatory responses and attenuating anti-inflammatory responses.