NEONATAL CALVES DEVELOP MORBIDITIES INCLUDING DIARRHEA AND SEPTICEMIA THAT INCREASE THEIR MORTALITY RISK. THE CAUSE IS INFECTION BY PATHOGENS SUCH AS ESCHERICHIA COLI AND THEIR ENDOTOXINS (I.E., LIPOPOLYSACCHARIDE) DUE IN PART TO AN UNDERDEVELOPED IMMUNE SYSTEM. A COMMON APPROACH TO RESOLVE INFECTION IS ANTIBIOTIC THERAPY; HOWEVER, ANTIBITOIC USE IS OFTEN MISMANAGED, MAY PROMOTE RESISTANT BACTERIA, AND IS A SOCIETAL CONCERN. THUS BY ADDRESSING THE EXPLORATORY RESEARCH PROGRAM AREA, OUR GOAL IS TO IDENTIFY A NOVEL NON-ANTIBIOTIC THERAPEUTIC TOOL THAT BOLSTERS IMMUNE FUNCTION AS A MEANS TO PREVENT MORBIDITY AND MORTALITY IN CALVES. A PROMISING SOLUTION THAT DESERVES IMMEDIATE ATTENTION IS THE USE OF LYSOPHOSPHOLIPIDS AS IMMUNOMODULATORS. IN HUMANS, LOW CIRCULATING CONCENTRATIONS OF LYSOPHOPHOLIPIDSARE PREDICTIVE FOR SEPSIS AND LYSOPHOPHOLIPID THERAPY PREVENTS EXPERIMENTAL SEPSIS-INDUCED MORTALITY IN RODENTS. THE MODE OF LYSOPHOPHOLIPID ACTION APPEARS TO INVOLVE ENHANCED NEUTROPHIL BACTERICIDAL ACTIVITY, SUPPRESSED ENDOTOXIN-MEDIATED INFLAMMATION, AND INCREASED ADAPTIVE IMMUNE CELL INTERFERON-Γ SECRETION AND ANTIBODY PRODUCTION. OUR PRELIMINARY DATA DEMONSTRATES THAT CIRCULATING LYSOPHOPHOLIPIDS ARE ALSO SUPPRESSED IN DAIRY CATTLE EXPERIENCING ENDOTOXEMIA; THEREFORE, WE HYPOTHESIZE THAT LYSOPHOSPHOLIPID THERAPY BOLSTERS IMMUNE FUNCTION IN A MANNER COMPARABLE TO NON-RUMINANTS TO PREVENT INFECTION IN YOUNG CALVES. AT CORNELL UNIVERSITY, A COLLABORATIVE TEAM WILL DETERMINE WHETHER LYSOPHOPHOLIPIDS ENHANCE NEUTROPHIL FUNCTIONALITY AND PROTECT AGAINST ESCHERICHIA COLI LIPOPOLYSACCHARIDE INFECTION IN PRE-WEANED HOLSTEIN HEIFER CALVES. EXPLORING THE ABILITY OF LYSOPHOPHOLIPIDS TO MODULATE IMMUNITY IN CALVES WILL ENABLE US TO DEVELOP NEXT-GENERATION THERAPEUTIC TECHNOLOGIES TO PREVENT MORBIDITY AND MORTALITY IN LIVESTOCK.

Cornell University, Ithaca NY

Investigators