الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 211 |  |  |
| | | from | 211 | | |
Abstract
Schistosomiasis is the second most important parasitic disease next to Malaria. Despite decades of intense efforts to control schistosomiasis, the disease is still one of the major health problems in Africa.
Schistosomes have developed many methods of down-regulating a human’s immune response. For this reason, it is difficult for an immune system to eliminate a schistosomiasis infection on its own.
Schistosomes release significant amounts of prostaglandin D2, which regulates various stages of the immune response and represent a strategy for the schistosomes to evade host immune defenses.
PGD2 binding to DP1 receptors,
- Suppresses Langerhans cells migration in the skin.
- Elevates cellular cAMP level.
- Inhibits IL-12 production by dendritic cells (DC).
- Inhibits IFN- production by T cells and NK cells.
So PGD2 can restrain Th1 functions. Hence, it can modulate the host inflammatory and immune responses.
In the present study, we aimed to block DP1 receptors during the skin phase of infection to ensure:
1- Fast departure of Langerhans cells to SLN and fast delivering of processed antigens to lymphocytes.
2- Activation of type 1 immune responses & innate reactions.
To investigate the role of PGD2 receptor blockers in the treatment of Schistosoma mansoni infection, we evaluated the effect of laropiprant (a selective DP1 blocker) on the elicited immunological response and investigated its immune-modulatory effect
when administered 2&4 mg/kg intra-peritoneally, 2 mg/kg topically or subcutaneously during early phase one hour before infection and after 24 hours then mice sacrificed 2 weeks and 4 weeks post infection.
Male C57BL/6 mice were infected with 100 cercariae by free percutaneous penetration method in intraperitoneal groups, or with 250 cercariae in topical groups using ring method and abdominal method and in subcutaneous groups using ring method.
Laropiprant has succeeded to neutralize PGD2 and activated type 1 immune response as evidenced by the significant increase in the ratio of IFN-γ/IL-4 after the treatment with 2 & 4 mg/kg (reaching 161.75 %, 191.34 % of control value respectively) in intraperitoneal groups.
Laropiprant has succeeded to reduce worm count (in a dose dependent manner after hepato-portal perfusion 28 days post-infection) reaching 35.71% and 31.55% at 4 mg/kg and 2 mg/kg respectively.
This reduction may be mediated by:
1- Induction of Th1 mediated activation of inflammatory cells such as macrophages, polymorph nuclear leukocytes, and natural killer cells, cytotoxic T lymphocytes that control vigorous innate reactions against the parasite in the skin & lung tissues.
2- Rapid induction of immune priming in the skin due to fast departure of antigen presenting cells to SLNs.
Finally we conclude that:
1- Laropiprant can be used efficiently as a protective agent against Schistosoma mansoni infection.
2- Laropiprant may be useful as Immuno-modulating substance to protect from various immune disorders in which Th2 responses are dominant.