INVESTIGATING INTERLEUKIN-18 INVOLVEMENT AND ITS MODULATORY EFFECTS ON MAJOR CYTOKINES RELEASE DURING MALARIA INFECTION IN MICE
| dc.contributor.author | HASBALLAH, KARTINI | |
| dc.date.accessioned | 2016-01-12T04:12:50Z | |
| dc.date.available | 2016-01-12T04:12:50Z | |
| dc.date.issued | 2010-10 | |
| dc.description.abstract | IL-18 is a potent pro inflammatory cytokine that plays multiple roles in immune' responses and inflammatory activities in many disease conditions, but its involvement in the underlying pathogenesis of malaria has not been fully elucidated. In this study, the role and involvement of IL-18 during malaria infection was investigated and the impact of its pathway modulation on the course of the infection and the major cytokines released during the infection was preliminary evaluated. Plasmodium berghei ANKA infection in ICR mice were used as malaria model througho~t the study. The animals were inoculated intravenously with 2 x 107 parasitized red blood cells (PRBCs) obtained from a donor mouse infected with the parasite. The control animals received an equivalent volume and dilution (0.2 mL, i.v.) of normal mouse RBC. Results demonstrated that the malarial mice showed sick behavioral. changes on day 4 after inoculation when the levels of parasitaemia were ~ 60% and then continued to increase until circulating parasitaemia reached around 80%. The infected mice succumbed to hyperparasitaemia 5-6 days after infection. ICR mice also showed significant decrease in body temperature and body weight during the peak parasitaemia. IL-18 concentrations in the plasma determined by means of ELISA, showed significant elevation thrOl~ghout the infection and a positive correlation with parasitaemia development. Since malaria infection causes multi organ dysfunction, tissues from major organs known to be affected during malaria infection which include the spleen, liver, brain, lungs and kidney were examined for IL-18 expression using SDS-PAGE and Western blot analysis. The study revealed that IL-18 was expressed in different intensity in the spleen, liver, brain and lungs. No IL-18 was detected in the kidney of mice during the infection. IL-18 production during malaria infection was modulated by treatment with rrnIL-18BP, ArnIL-18 and rrnIL-18. Treatment with rrnIL-18BP and ArnIL-18 inhibited the parasitaemia development at early phase of infection. Significant inhibition on parasites' development occurred on day 1 until day 3 after treatment. Body weight as well as body temperature of malarial mice decreased on day 4 until day 6 from thei~ initial values after the treatment. rrnIL-18 treatment caused the parasitaemia levels to increase rapidly followed by a decrease in body weight and body temperature. Earlier mortality was also observed in the malarial mice treated with rrnIL-18. Results also showed that inhibition ofIL-18 by treatment with rrnIL-18BP and ArnIL-18 significantly reduced the release of pro-inflammatory cytokines IFNy, TNFa, IL-6 and IL-la levels and on the other hand increased the level of anti-inflammatory cytokine IL-IO significantly. In contrast, augmentation of IL-18 production significantly increased the levels of the proinflammatory cytokines and reduced the level of the anti-inflammatory cytokine in the serum during the infection. In conclusion, the results from this study suggest that IL-18 is involved during malaria infection and it may well playa crucial role in mediating the severity of the disease. Its pathway modulation produced a significant impact on the cytokine network during the infection which may suggest that modulating IL-18 production during malaria infection could be a promising therapeutic concept for malaria therapy. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/1536 | |
| dc.subject | INVESTIGATING INTERLEUKIN | en_US |
| dc.subject | INFECTION IN MICE | en_US |
| dc.title | INVESTIGATING INTERLEUKIN-18 INVOLVEMENT AND ITS MODULATORY EFFECTS ON MAJOR CYTOKINES RELEASE DURING MALARIA INFECTION IN MICE | en_US |
| dc.type | Thesis | en_US |
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