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Title: The effect of Anti-TNF-α Antibody on Leishmania major Infection as to Hyperalgesia and the Cytokine Interplay
Other Titles: The effect of anti-TNF-α antibody on Leishmania major infection as to hyperalgesia & the cytokine interplay
Authors: Salman, Sara 
Advisors: Karam, Marc 
Subjects: Leishmania
Anti-Inflammatory Agents
Issue Date: 2015
Cutaneous Leishmaniasis is a disease caused by the flagellated promastigote form of the Leishmania major parasite. The infection of the susceptible BALB/c mice with a high dose of this intracellular parasitic protozoan induces a sustained hyperalgesic response accompanied by up-regulation of the pro-inflammatory cytokines Interleukin-1β (IL-1β) and Interleukin-6 (IL-6). Interleukin-13 (IL-13) has been shown to reduce this hyperalgesia when IL-6 levels are increased and to reduce IL-1β levels during and after the treatment period. These observations imply that cytokine signaling cascades lead to the production of sympathetic amines via TNF-α and Keratinocyte Derived Chemokine (IL-8-like analogue) but not via prostaglandins. However, the role of TNF-α in L. major- induced hyperalgesia and its mechanism of action have not been elucidated. This study investigates the effects of anti TNF-α monoclonal antibody (Infliximab) on L. major-induced inflammation and hyperalgesia in mice and examines the levels of several inflammation-related cytokines. High doses of L. major parasites were injected in L. major susceptible BALB/c mice in the presence of Anti-TNF-α . The Hot Plate and Tail Flick tests were used to examine hyperalgesia and results showed that Anti-TNF-α significantly reduces L. major-induced hyperalgesia in a dose-dependent manner. The effects of anti-TNF-α injections on the cytokine levels were assessed using ELISA kits. Compared to control mice, TNF-α neutralization up-regulated "anti-inflammatory cytokines" such as IL-10 and downregulated "pro-inflammatory cytokines" such as IL-1β and IFN-γ. In addition, novel roles of IL-17 and KC in limiting leishmaniasis progression and hyperalgesia were established. Finally, the course of the infection was assessed via parasite burden and regression of parasite growth was observed in Anti-TNF-α antibody treated mice. Taken together, L. major-induced hyperalgesia was shown to be mediated by TNF-α which in turn may have a potential role in enhancing leishmaniasis progression in susceptible hosts.
Includes bibliographical references (p.59-75).

Supervised by Dr. Marc Karam.
Rights: This object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the personal and educational use exceptions must be obtained from the copyright holder
Ezproxy URL: Link to full text
Type: Thesis
Appears in Collections:UOB Theses and Projects

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