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International Journal of Pharmacology

Year: 2014  |  Volume: 10  |  Issue: 7  |  Page No.: 389 - 397

Mitigation of Septic Signs by Pravastatin during LPS Co-Administered Hen-Egg White Lysozyme Immunization in Mice

M. Yaqoob Wani, Tapas Kumar Goswami, Divya Chaudhary, Rajendra Singh and Kuldeep Dhama

Abstract

Lipopolysaccharide is the most important component of Gram negative bacteria that activates immune system through TLR-4 pathway. In the present study, the adjuvant effects of Pasturella multocida 52 strain (Pm52) on Hen Egg-white Lysozyme (HEL) and the possible attenuation of septic signs by pravastatin were investigated. In vitro results showed that Pm52 LPS stimulates nitric oxide (NO) production from splenocytes in time and dose dependent manner where as pravastatin (10 μM) inhibited the LPS induced NO production to basal levels (p<0.05). Furthermore, presence of pravastatin (10 μM) does not inhibit the in vitro proliferative responses of splenocytes by graded doses of Pm52 extracted LPS. The co-administration of Pm52 LPS with HEL by subcutaneous route in mice significantly increased TNF-α and NO levels at 2 and 6 h, respectively, as well as the HEL specific IgG development at 14th day Post Inoculation (PI). Administration of pravastatin by intraperitoneal route significantly reduced serum TNF-α and NO levels, the pro-inflammatory mediators responsible for induction of septic shock as well as stabilized TNF-α: IL-10 ratio without affecting HEL specific adaptive immune responses. However, further studies are required in this direction to determine the long term immune modulating effects of LPS and pravastatin on the host animals so as to be used in a beneficial way.

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