The effects of equine plasma transfusion on markers of inflammation in healthy neonatal foals
Very few studies in veterinary medicine have investigated the immunologic changes and inflammatory markers associated with transfusion of fresh frozen plasma in neonatal foals. Plasma transfusion is routinely used in the equine neonate for several reasons ranging from prophylaxis of disease to complementary treatment of ongoing conditions. Previous studies in hospitalized sick neonatal foals have reported a transfusion reaction rate close to 10% (Hardefeldt, 2010). In this prospective study, we examined the immunological impact of intravenous (IV) fresh frozen plasma administration in healthy newborn foals, using a three-fold approach. Systemic, plasma-invoked immune and inflammatory responses were assessed by measuring 1) peripheral blood leukocytes cell cytokine gene expression, 2) circulating cytokine concentration (interferon-gamma [IFN-γ], interleukin- 1β [IL-1 β], tumor necrosis factor-α [TNF- α], interleukin-6 [IL-6], interleukin-10 [IL-10] and interleukin-8 [IL-8], interleukin-4 [IL-4], interleukin-17 [IL-17]), and 3) changes in acute phase protein (fibrinogen [FIB] and serum amyloid A [SAA]) production. A total of 35 healthy, neonatal foals (mean ± SD age 34 ± 5 hours) were randomly allocated into one of two groups, and given either hyperimmune, fresh frozen plasma (treatment) or crystalloids (control) by IV administration through a preplaced jugular catheter. Blood samples were collected before (hour 0) treatment and at 2, 6 and 24 hours after transfusion. Serum cytokines concentrations were measured with either bead based multiplex technology (IFN-γ, IL-4, IL-17, IL-10) or with commercial ELISA kits (IL-6, IL-8 and IL-1β, TNF- α, IL-10). Peripheral blood leukocyte gene expression was performed with qRT-PCR. Serum amyloid A [SAA] was measured with turbidometric immunoassay and fibrinogen concentration [FIB] was determined with the method of Clauss. Comparisons between groups were made using a Kruskal Wallis test, and changes overtime within groups were analyzed with Friedman’s test followed by Mann Whitney U. Parametric data was analyzed with repeated measures ANOVA with LSD correction. Plasma administration was associated with a significant decrease in TNF-α gene expression between 6 and 24 hours (p= 0.007) and IL-1ß gene expression at 24hrs. Crystalloid administration was associated with a significant decrease in IL-1ß (p<0.005) and IL-10 (p=0.003) gene expression at 24hrs. In foals receiving plasma a significant increase from time 0 in serum [TNF- α] at 2, 6 and 24 hours (p<0.001) and in [IL-8] at 2 hours (p=0.001) was noticed. [IL-6] in plasma group was greater compared to the crystalloid group at 6 hours (p=0.051) and 24 hours (p=0.044). No significant overtime differences or between group variations were noticed for the other cytokines. A greater number of foals in the plasma group demonstrated an increase in [TNF- α], [IL-8] and [IL-6] compared to control group. On the contrary more foals in the control group demonstrated an increase over time of [IL-17] and [IL-4]. [FIB] was significantly different (p=0.048) between plasma and crystalloid groups at 6 hours, while [SAA] was different at 24 hours between groups (p=0.0125). In foals receiving plasma, [FIB] was significantly increased at 2, 6 and 24 hours (p<0.001) compared to baseline. We concluded that plasma transfusion in healthy foals leads to quantifiable changes in concentrations of these cytokines and that commercially available plasma may influence foals [FIB] soon after transfusion. Inflammation was also found in the foals receiving crystalloids and an effect of catheterization and fluid shear force was hypothesized. In combination, these results indicate that IV crystalloid and plasma administration are associated with a significant, but clinically undetectable, systemic inflammatory response. The nature of this immunological response was qualitatively different and quantitatively greater in foals receiving IV plasma. Further studies are required to elucidate the mechanism and significance of this transfusion- associated systemic immune response, and to determine how this might be different in sick or compromised individuals.
Foal, Equine, Fresh Frozen Plasma: Cytokines, Acute phase proteins
University of Illinois - Urbana-Champaign
Networked Digital Library of Theses and Dissertations
University of Illinois at Urbana-Champaign