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Polyinosinic-polycytidylic acid having long-term unfavorable influence on anti-bacterial defense mechanism

A polysinosinate, defense mechanism technology, applied in the field of long-term adverse effects of polysinosinate on the antibacterial defense mechanism of the lungs

Inactive Publication Date: 2017-05-31
宁波美丽人生医药生物科技发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Furthermore, the deleterious effects of polyinosinic acid may be mediated by type I interferons

Method used

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  • Polyinosinic-polycytidylic acid having long-term unfavorable influence on anti-bacterial defense mechanism
  • Polyinosinic-polycytidylic acid having long-term unfavorable influence on anti-bacterial defense mechanism
  • Polyinosinic-polycytidylic acid having long-term unfavorable influence on anti-bacterial defense mechanism

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Polyinosinogenic acid increases susceptibility of lung tissue to bacteria

[0061] We first examined the effect of polysinosinate administration on bacterial clearance following bacterial infection. Experimental animals receive intranasal administration of polyinosine or imiquimod for two consecutive days (eg, double dose). On the third day (ie, 24 hours after the last polyinosinate dose), animals were injected intrathecally with S. pneumoniae. We found a significant increase in bacterial counts in the lungs of animals administered nasal polyinosinosinate. Interestingly, imiquimod or gademotel (TLR7 agonists such as figure 1 A) There was no significant difference in bacterial clearance between the treatment groups. But both groups showed robust clearance during the initial challenge phase. Administration of TLR7 ligand alone was therefore not sufficient to reduce bacterial clearance.

[0062] Second, we examined whether polyinosinogenic acid also reduced the clear...

Embodiment 2

[0064] The degree of impairment of bacterial clearance is directly proportional to the duration of polyinosarglycine administration

[0065] We observed a time point at which the rate of bacterial clearance in animals decreased after administration of polyinosinogenic acid. Since viral infections, such as influenza, usually last for several days or even longer, we conducted related experimental studies, taking polyinosinogenic acid in 1 dose or 3 doses to simulate the effect of viral infection. After 24 hours of intranasal administration of polyinosinogenic acid or saline once or three times, the experimental animals were intrathecally injected with Streptococcus pneumoniae. At 48h, record the amount of bacteria in the body. We found that the dose of polysarcocytate correlates with the rate of bacterial clearance. The bacterial clearance rate in the experimental animals with one-time administration of polyinosinic acid will tend to decrease (the average CFU value is 8 times ...

Embodiment 3

[0067] TLR3 and Cardif pathways enhance host susceptibility to bacteria induced by polyinosinogenic acid

[0068] Since polysinosine activates both TLR3 and the Cardif-dependent helicases RIG-I and MDA5, we sought to determine whether either or both pathways are involved in polysinosine impairing host bacterial clearance. For such studies, we use polyinosinogenic acid in animals lacking TLR3 (Tlr3- / -), Cardif (Cardif- / -), or both (double knockout). Cardif acts as an adapter molecule for RIG-I and MDA5 signaling early in the antiviral response [25][26][27][28] . We found that TLR3 (Tlr3- / -) deletion or Cardif (Cardif- / -) experimental animals had improved bacterial clearance rate after administration of polyinosinogenic acid. Compared with the normal saline group, the double knockout (Cardif- / - / Tlr3- / -) group was administered with polyinosinogenic acid under the environment of secondary bacterial infection, and the bacterial clearance rate in the body was significantly improve...

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Abstract

The invention relates to the field of biological medicine, and especially relates to polyinosinic-polycytidylic acid having long-term unfavorable influence on an anti-bacterial defense mechanism. According to the invention, after bacteria infection, influence of polyinosinic-polycytidylic acid administration on bacteria clearance and animal lung bacteria amount of polyinosinic-polycytidylic acid administration are obviously increased, polyinosinic-polycytidylic acid enhances the susceptibility of bacteria on lung tissue, a proportional relation of damage degree on bacteria removing force and continuous time of the proportional relation administration is established, and the polyinosinic-polycytidylic acid has influence on anaphase bacteria removing force. The long-term unfavorable influence of polyinosinic-polycytidylic acid on the lung antibiosis defense mechanism is confirmed.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the long-term adverse effect of polyinosinogenic acid on the antibacterial defense mechanism of the lungs. Background technique [0002] Viral infections of the respiratory tract are common respiratory diseases and often present with a benign clinical course. However, a significant proportion of patients develop concomitant or secondary bacterial infections [1][2][3] , this complication can lead to respiratory failure or death. Although children, the elderly, and the immunocompromised population are at high risk for outbreaks of these complications, viral bacterial pneumonia can also occur in healthy adults and result in a significant disease burden. Viral-bacterial pneumonia has been repeatedly reported following the prevalence of influenza infection. It was the leading cause of death in patients during the influenza epidemics of the 20th century and the 2009 H1N1 influenza pandemi...

Claims

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Application Information

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IPC IPC(8): A61K49/00
CPCA61K49/0004
Inventor 田晓丽
Owner 宁波美丽人生医药生物科技发展有限公司
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