Advisor

Willeford, O. Kenneth

Committee Member

Brown, Ashli

Committee Member

Peebles, David E.

Committee Member

Willard, Scott

Committee Member

Pharr, Todd

Date of Degree

8-1-2010

Document Type

Dissertation - Open Access

Major

Molecular Biology

Degree Name

Doctor of Philosophy

College

College of Agriculture and Life Sciences

Department

Department of Biochemistry and Molecular Biology

Abstract

Immune Cell Potentiating Factor (ICPF) represents a class of biological response modifiers initially only found within active caprine serum fractions. Controlled studies have since demonstrated active ICPF derived from several non-caprine mammalian sources; including equine and human. ICPF is able to increase survivability in murine gram negative induced sepsis (60%) as well as secondary infection and subsequent sepsis in canines infected within canine parvo virus 2 (36%) despite showing no innate antiviral properties. ICPF is able to initiate systemic proteomic changes within several organ systems; including serum, liver, brain, lung, and spleen. ICPF initiated an early acute phase response, specifically through the increased expression of serum amyloid A, with systemic serum levels increasing from 1.5 μg/mL to 403.0 μg/mL within 24 hours and increased to 3,400 μg/mL within 48 hours following ICPF administration. Evaluation of cytokine expression following ICPF treatment revealed the up-regulation of IL-6, INF-γ, and the chemokine CXCL1\KC in vivo as well as the expression of IL-6 and IFN-γ in vitro within 3 hours of treatment. Development of an in vitro bioassay through the expression of IL-6 and IFN-γ within whole blood and peripheral blood mononuclear cells will allow for further elucidation and testing of ICPF outside of an animal host. The early expression of proinflammatory cytokines and chemokines, an acute phase response including serum amyloid A, and ICPF’s inability to alleviate mortality in a lipopolysaccharide animal mortality model strongly indicates an active role for ICPF as an immune regulatory peptide capable of promoting an early inflammatory response to Salmonella enterica serovar Typhimurium thereby reducing the risk and mortality associated with sepsis.

URI

https://hdl.handle.net/11668/15440

Comments

Biological Response Modifier||Caprine||Immune Cell Potentiating Factor

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