** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** PARTURITION IS A RISKY PERIOD WHEN THE INCIDENCE OF DISEASE IS HIGH IN DAIRY COWS. THESE DISEASES INCLUDE BOTH METABOLIC (KETOSIS, DISPLACED ABOMASUM, HYPOCALCEMIA, AND RETAINED PLACENTA) AND INFECTIOUS DISEASES (MASTITIS AND METRITIS). ACCORDING TO THE USDA 2007 NAHMS REPORT, 37% OF COWS EXPERIENCE AT LEAST ONE DISORDER DURING THE POSTPARTUM PERIOD. THESE DISEASES ARE QUITE COSTLY. TO PROVIDE AN EXAMPLE OF THIS, THE COST OF CLINICAL MASTITIS DURING EARLY LACTATION IS ESTIMATED AT $444 PER CASE, AND THE ANNUAL COST OF MASTITIS FOR THE US DAIRY INDUSTRY IS ESTIMATED AT $2 BILLION. AS SUCH, INNOVATIVE ANIMAL HEALTH SOLUTIONS WILL BE REQUIRED TO SOLVE COMPLEX PROBLEMS IN AN ECONOMICALLY STRAINED DAIRY INDUSTRY. IN THIS RESEARCH PROPOSAL, WE STRIVE TO IMPROVE OUR UNDERSTANDING OF THE NEXUS BETWEEN SYSTEMIC INFLAMMATION AND MAMMARY GLAND HEALTH IN PERIPARTURIENT DAIRY CATTLE.THE OBJECTIVE OF THIS PROPOSAL IS TO ELUCIDATE THE DIRECT EFFECTS OF CHRONIC LOW-GRADE SYSTEMIC INFLAMMATION ON MAMMARY GLAND HEALTH. ELEVATED CONCENTRATIONS OF INFLAMMATORY MARKERS DURING THE PERIPARTUM PERIOD HAVE BEEN ASSOCIATED WITH DISEASES INCLUDING MASTITIS DURING THE POSTPARTUM PERIOD IN DAIRY CATTLE. NEVERTHELESS, THESE ASSOCIATIONS DO NOT NECESSARILY DEMONSTRATE A CAUSAL RELATIONSHIP. WE HYPOTHESIZE THAT LOW-GRADE SYSTEMIC INFLAMMATION WILL IMPAIR MAMMARY GLAND IMMUNE RESPONSES AND INCREASE SEVERITY DURING AN INTRAMAMMARY CHALLENGE.THEREFORE, IN AIM 1, WE PROPOSE TO STUDY THE ROLE OF CHRONIC, LOW-GRADE SYSTEMIC INFLAMMATION IN POSTPARTUM DAIRY CATTLE ON MAMMARY GLAND IMMUNE RESPONSES DURING AN INTRAMAMMARY STREPTOCOCCUS UBERIS CHALLENGE. FOR THIS OBJECTIVE, WE WILL USE RECOMBINANT TUMOR NECROSIS FACTOR Α AS A MODEL PRO-INFLAMMATORY CYTOKINE TO INDUCE CHRONIC, LOW-GRADE INFLAMMATION. FOR AIM 2, WE PROPOSE TO ASSESS THE EFFECTS OF POSTPARTUM ADMINISTRATION OF MELOXICAM, A NON-STEROIDAL ANTI-INFLAMMATORY DRUG USED TO INHIBIT POSTPARTUM SYSTEMIC INFLAMMATION, ON MAMMARY GLAND IMMUNE RESPONSES DURING AN INTRAMAMMARY STREPTOCOCCUS UBERIS CHALLENGE. WE ANTICIPATE THAT SYSTEMIC INFLAMMATION WILL IMPAIR MAMMARY GLAND IMMUNE RESPONSES LEADING TO A MORE SEVERE INTRAMAMMARY INFECTION, WHEREAS POSTPARTUM MELOXICAM ADMINISTRATION WILL IMPROVE MAMMARY GLAND IMMUNE RESPONSES LEADING TO AN ENHANCED ABILITY TO CONTROL AND ELIMINATE THE STREPTOCOCCUS UBERIS.THE PROPOSED STUDY WILL DEFINE FOR THE FIRST TIME THE IMPACT OF SYSTEMIC INFLAMMATION ON MAMMARY GLAND IMMUNE RESPONSES. POSTPARTUM DAIRY CATTLE EXPERIENCE CHRONIC, LOW-GRADE SYSTEMIC INFLAMMATION, WHICH HAS BEEN ASSOCIATED WITH DISEASE INCIDENCE. NEVERTHELESS, IT IS UNCLEAR IF THIS SYSTEMIC INFLAMMATORY RESPONSE IS PROTECTIVE OR PATHOLOGICAL. AS SUCH, IT HAS BEEN INCREDIBLY CHALLENGING TO DEVELOP SOLUTIONS FOR POSTPARTUM DISORDERS BECAUSE WE DO NOT UNDERSTAND THE PATHOLOGY OF MANY OF THESE DISORDERS AND DISEASES. THEREFORE, IT COMES AS NO SURPRISE THAT THE INCIDENCE OF MANY CLINICAL DISEASES DURING THE POSTPARTUM PERIOD INCLUDING,CLINICAL MASTITIS HAVE STUBBORNLY REMAINED UNCHANGED OVER THE PAST FEW DECADES. FUTURE RESEARCH PROJECTS ARE NEEDED TO DEVELOP SOLUTIONS FOR POSTPARTUM HEALTH PROBLEMS; HOWEVER, THESE PROJECTS MUST BE INFORMED BY STUDIES EVALUATING THE CAUSES OF THESE DISORDERS TO IDENTIFY POTENTIALLY EFFECTIVE TREATMENT STRATEGIES. THE RESULTS FROM THESE STUDIES WILL BE USED TO INFORM FUTURE RESEARCH PROJECTS TO DEVELOP SOLUTIONS TO REDUCE THE INCIDENCE OF POSTPARTUM DISORDERS INCLUDING MASTITIS. THE LONG-TERM GOALS OF THESE PROJECTS ARE TO IMPROVE DAIRY CATTLE HEALTH AND REDUCE ANTIMICROBIAL USAGE.

South Dakota State University, Brookings SD

Investigators