Spray-dried plasma (SDP), spray-dried serum (SDS), or globulin concentrate are ingredients that are collected and processed to preserve the functional characteristics of the proteins. These functional proteins (spray-dried plasma, serum, or globulin concentrate) are a diverse mixture of components consisting of immunoglobulins, albumin, fibrinogen, lipids, growth factors, biologically active peptides (defensins, transferrin), enzymes, and other factors that have specific biological activities within the intestine independent of their nutritional value. Spray-dried plasma is primarily used as an ingredient blended into dry feed or milk replacers. Spray-dried serum and globulin concentrate are ingredients used in colostrum supplements/replacers and/or other liquid feeding applications.
Spray-dried plasma is used extensively in nursery pig feed to enhance feed intake, growth, and feed efficiency during the post-weaning period. The beneficial effects of SDP are more pronounced under production conditions with high pathogen exposure than with low pathogen exposure. Numerous studies involving challenge with pathogenic bacteria, viruses, or protozoa have demonstrated reduced mortality and morbidity with feeding spray-dried animal (bovine or porcine) plasma to various animal species (swine, calves, poultry, shrimp).
Several modes of action of SDP have been proposed. Collectively, these proposed actions suggest that oral consumption of SDP may conserve immune response resources through interactive mechanisms between the intestine and other immune system tissues. The purpose of this review is to focus on SDP’s effect on the animal’s immune system and how it may be utilized in economically important applications of calf production.
Mechanisms of Spray-Dried Plasma
Literature reviews (Coffey and Cromwell, 2001; van Dijk et al., 2001) indicate that consumption of SDP by weanling pigs results in an average improvement in body weight gain, feed intake, and feed efficiency of 25, 21, and 4%, respectively. The magnitude of growth and feed intake response to SDP is difficult to explain as purely a nutritional effect. Ermer et al. (1994) reported that both palatability and feed intake were improved when pigs were fed diets containing SDP compared to dried skim milk, suggesting that SDP improved feed intake and growth simply because it was more palatable. However, Jiang et al. (2000ab) reported that feeding SDP to pigs that were fed the same amount of feed per day as control pigs improved efficiency of dietary protein utilization. Furthermore, the researchers noted that SDP reduced cellularity of the lamina propria of the small intestine, suggesting reduced local inflammation.
The beneficial effects of SDP are more pronounced under production conditions with high pathogen exposure than with low pathogen exposure (Stahly et al., 1994; Coffey and Cromwell, 1995). Similar observations have been reported in broilers (Campbell et al., 2003) and turkey poults (Campbell et al., 2004a). Numerous studies (Table 1) involving challenge with pathogenic bacteria (E. coli, Salmonella, Pasteurella multocida), viruses (rotavirus, coronavirus, white spot syndrome virus) or protozoa (Cryptospirosis parvum) have demonstrated reduced mortality and morbidity when feeding spray-dried animal (bovine or porcine) plasma to various animal species (swine, calves, poultry, shrimp). These results suggest that SDP reduces attachment, adhesion, and replication of the organism (antigen-antibody interactions), facilitates tissue repair, or reduces the overall inflammatory response.
More recent evidence supports the concept that oral consumption of SDP maintains gut barrier function and reduces or modulates the overstimulation of the inflammatory response. Touchette et al. (2002) reported reduced cytokine mRNA expression (TNF-a, IL-1ß, and IL-6) in multiple tissues (hypothalamus, pituitary, adrenal, spleen, thymus, and liver) of pigs orally consuming SDP and challenged with lipopolysaccharide (LPS). Bosi et al. (2004) reported that feeding SDP to pigs challenged with enterotoxigenic E. coli K88 reduced inflammation as indicated by improved growth, reduced salivary IgA secretion, decreased intestinal mucosal damage, and reduced pro-inflammatory cytokine expression in the gut. They concluded that SDP protects against E. coli K88 infection by maintaining mucosal integrity, enhancing specific antibody defense, and decreasing inflammation in the intestine.
Influence of SDP on Intestinal Inflammation and Gut Barrier Maintenance
Intestinal inflammation results in a cascade of events including edema, leukocyte infiltration, vasodilatation, reduced nutrient absorption, increased epithelial permeability due to altered barrier function, and immune system activation. To better understand the effects of SDP on specific immune responses, Pérez-Bosque et al. (2004) developed a rat model for evaluating impact of SDP during intestinal inflammation. Rats were challenged with a superantigen, Staphylococcus aureus enterotoxin B (SEB). While the SEB challenge activated the immune system, feed intake and growth rates were unaffected, indicating the inflammation was mild. The researchers reported less fecal water content, reduced γδ-T lymphocytes, and reduced percentage of cytotoxic cell populations in organized gut associated lymphoid tissue (GALT) populations (i.e., Peyer’s patches) of rats fed SDP and challenged with SEB. By measuring a reduction in expression of the intestinal sodium glucose transporter 1 (SGLT1), it was estimated that SEB reduced glucose absorption by 8 to 9% (Garriga et al., 2005). Spray-dried plasma ameliorated the SEB-induced reduction in SGLT1 expression suggesting an improvement in nutrient absorption.
Intestinal permeability was evaluated by Pérez-Bosque et al. (2006) using the same SEB challenge model. Challenge with SEB resulted in increased intestinal permeability during intestinal inflammation as assessed by both structural [reduction of tight junction (ZO-1) and adherent junction (ß-catenin) proteins] and functional measurements [increased intestinal flux of horseradish peroxidase (HRP) and dextran]. Dietary supplementation of SDP reduced the effects of SEB by reducing dextran and HRP paracellular flux across the intestinal epithelium. These data indicate that SDP supplementation reduces inflammation-induced damage of epithelial structure, thus improving intestinal mucosal barrier function.
Stress and antigen exposure activates the immune system and stimulates pro-inflammatory cytokines, which reduces motivation to eat (Kent et al., 1996) and interacts with growth hormone and insulin-like growth factor (IGF-1) to suppress cell growth (Kelly, 2004). The more recent evidence that SDP reduces the overstimulation of pro-inflammatory cytokines strongly suggests that this is an additional mechanism of action of SDP in restoring feed intake of animals and reducing the deleterious effects of disease and other stressors. Inflammatory events occur throughout the life cycle of animals, and use of SDP to affect the inflammatory response in applications beyond the weanling period is now being explored.
Spray-Dried Plasma and Productive Functions of Calves
Pre-Gut Closure Application: Calf health and survival affect the economics of dairy operations. The ability to reduce the incidence of failure of passive immunity (FPT) and improve productive functions such as growth, survival, and feed efficiency are of value to the producer. Colostrum supplements/replacers have been developed to reduce the incidence of FPT by providing absorbable immunoglobulin for the neonatal calf when fed alone or added to maternal colostrum.
Arthington et al. (2000) fed calves colostrum of varying IgG content with differing amounts of SDS within 4 h of birth in order to provide equal mass of IgG intake (96 to 99 g of IgG). Twelve hours after feeding, mean serum IgG concentrations were 6.7, 10.3, and 10.7 g/L for calves fed high-quality colostrum, medium-quality colostrum plus SDS, and low-quality colostrum plus SDS, respectively. Thus, the use of SDS as a supplement to medium- or low-quality colostrum was an effective tool for providing additional IgG content to improve subsequent transfer of passive immunity.
Colostrum replacers were developed to be provided when good-quality colostrum is unavailable. Generally, colostrum replacers contain > 100 g of IgG/dose and provide additional nutrients for the calf (Quigley et al., 2002). Several studies have been conducted to assess the absorption of IgG from calves fed only a colostrum replacer formula. Jones et al. (2004) fed 78 calves either pooled maternal colostrum or a colostrum replacer containing globulin concentrate derived from bovine serum. Calves were fed an equal amount of IgG. Concentration of IgG at 24 h of age was similar between treatments and averaged 13.78 and 13.96 g/L for maternal colostrum and colostrum replacer, respectively. Additionally, fecal scores and body weights to 29 d of age were unaffected by treatment. Hammer et al. (2004) fed 150 g of IgG in either a single dose soon after birth or two doses 7 h apart. Calves fed the 150 g of IgG soon after birth had greater 24 h plasma IgG (13.0 vs. 10.3 g of IgG/L) and efficiency of absorption (35 vs. 30%) compared to two doses, indicating greater absorption and reduced FPT when fed the total mass soon after birth. Campbell et al. (2007) fed varying levels from 130 to 190 g of IgG in a single dose within 1 h of birth. Increasing IgG mass of the colostrum replacer resulted in a linear increase in 24 h serum IgG (11.6 to 14.3 g/L) and a linear decrease in AEA of IgG (31.5 to 26.6%). Collectively, the results indicate that colostrum supplement and replacers utilizing functional proteins can reduce the incidence of FPT and improve circulating IgG levels.
Post-Gut Closure Application: Immune activation due to various stressors (i.e., disease challenge, commingling, heat stress, weaning, etc.) can affect economically important production functions such as growth, lean tissue deposition, reproduction, and lactation. Depending on the degree of immune activation and/or stress, animals may experience reduced growth (Johnson, 1997; Spurlock 1997). Maintenance of intestinal barrier function may partially reduce activation of the immune system, thereby reducing losses associated with various stressors.
The use of SDP to reduce the effects of enteric challenges has been evaluated by several researchers. Quigley and Drew (2000) challenged 36 colostrum-deprived Holstein bull calves with E. coli K99 at 3 d of age. Calves were fed commercial calf milk replacers containing no additive, an antibiotic (neomycin and oxytetracycline), or SDP at 3.3% of the formula. All calves showed signs of enteric infection following oral challenge; however, calves fed either antibiotic or SDP had lower mortality and morbidity (number of days with diarrhea) than calves fed the control milk replacer. Based on attitude score, calves consuming SDP or antibiotic were more active and vigorous.
Hunt et al. (2002) orally challenged 24 calves with 108 oocysts of Crytosporidium parvum at 8 d of age. Calves were fed either soy protein concentrate or SDS in a milk replacer. Oral challenge caused significant fecal shedding of C. parvum oocysts, diarrhea, increased intestinal permeability, reduced villous surface area, and reduced intestinal lactase activity. Calves consuming SDS had a 33% reduction in oocyst shedding, 33% reduction in peak diarrheal volume, 30% reduction in total intestinal permeability, 15% increase in villous surface area, and more rapid recovery following challenge. The authors concluded that SDS reduced the effects of C. parvum by reducing the number of viable parasites, facilitating intestinal repair, and reducing attachment and replication of the infection.
Arthington et al. (2002) fed 12 Holstein bull calves milk replacer containing 0 or 160 g/d of an additive containing SDS as a therapy following oral challenge with bovine coronavirus on d 0. Feeding the additive containing SDS improved average packed cell volume, respiration rate, and feed intake compared to calves fed diets without the additive containing SDS. The authors concluded that supplementation of milk replacer with the additive containing SDS improved rate of recovery in calves following coronavirus challenge.
Quigley et al. (2002) reported the effects of feeding SDP or an additive containing bovine SDS, fructooligosaccharides, and minerals/vitamins in two studies utilizing 240 Holstein bull calves purchased from sale barns and dairy farms. Calves were usually within one week of age and in various stages of failure of passive transfer. In experiment 1, calves fed additive containing bovine SDS tended to have fewer days with diarrhea, lower use of electrolytes, and improved BW gain from d 29 to 56. Addition of SDP to milk replacer did not influence any parameter measured. In experiment 2, calves fed additive containing bovine SDS or milk replacer containing SDP had lower mortality (4.4 vs. 20%) and tended to have improved fecal scores and fewer days with scours. Antibiotic use was lower when calves were fed the SDS additive. Indices of enteric health (incidence of scours and treatment with antibiotics and electrolytes) were improved when SDP was added to milk replacer throughout the milk feeding period or as a serum additive during the first 15 d of the milk feeding period, when calves were most susceptible to enteric pathogens. The primary difference between experiments 1 and 2 was the overall level of stress. Calves used in experiment 1 were purchased from more dairy farms than sale barns and the experiment was conducted at an optimal time of the year (i.e., weather closest to the thermoneutral zone), CMR contained all milk protein, and there was a general lack of enteric challenge. Conversely, experiment 2 was conducted during a cold period of the year, the calves were fed CMR containing soy protein, and clinical symptoms related to enteric and respiratory pathogens occurred during the trial. Generally, these data suggest that calves fed SDP — whether as SDP in the CMR or as a serum additive — will respond to SDP, particularly when the overall level of challenge is significant.
Quigley et al. (2003) also reported about bovine- or porcine-derived SDP added to calf milk replacer. The milk replacers were formulated to contain whey protein concentrate (WPC) as the primary protein source or WPC plus 5% spray-dried bovine or porcine plasma. Intake, change in body weight, feed efficiency, morbidity, and mortality were determined. Mortality was 25, 7.5, and 5% in calves fed WPC, spray-dried bovine or porcine plasma treatments, respectively. Morbidity, measured as the number of days that calves had diarrhea, was reduced by about 30% when spray-dried bovine or porcine plasma was fed. Calves had diarrhea for 6.4, 3.9, and 4.7 d during the 42-d study when fed milk replacer containing WPC, spray-dried bovine or porcine plasma, respectively. Fecal scores tended to be reduced, and feed efficiency tended to be improved when spray-dried bovine or porcine plasma was fed. Mean body weight gains from d 0 to 42 were 231, 261, and 218 g/d for calves fed WPC, spray-dried bovine or porcine plasma, respectively. Overall, inclusion of spray-dried bovine or porcine plasma in milk replacer reduced morbidity and mortality of milk–fed dairy calves.
In summary, the use of SDP is well accepted in animal agriculture. Spray-dried plasma and/or spray-dried serum reduce the overstimulation of the immune response in animals, thereby conserving nutrient utilization for supporting the immune response and allowing nutrients to be utilized for productive purposes. Similar effects of SDP or SDS on inflammation and intestinal barrier function as noted in rats may be occurring in other animals. Research continues to elucidate the important role of these functional proteins in SDP in animal agriculture.
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Table 1. Summary of results from experimental challenges using SDP.
|Pigs||E. coli||↓fecal score||Borg et al.||1999|
|Pigs||Salmonella||↓fecal score||Borg et al.||1999|
|Pigs||E. coli||↑ADG, ↓mortality||Bosi et al.||2001|
|Pigs||E. coli||↑ADG, ↓IgA||Bosi et al.||2004|
|Pigs||E. coli||↑ADG, ↑Lactobaccili||Torrallardona et al.||2003|
|Pigs||E. coli||↑ADG||Campbell et al.||2001|
|Pigs||E. coli||↓shedding||Deprez et al.||1996|
|Pigs||Rotavirus||↓diarrhea||Corl et al.||2007|
|Pigs||E. coli||↓fecal score||Nollet et al.||1999a|
|Pigs||LPS||↓cytokine mRNA expression||Touchette et al.||2002|
|Pigs||E. coli||↑ADG||Campbell et al.||2001|
|Pigs||E. coli||↑ADG, ↓fecal score||Van Dijk et al.||2002|
|Pigs||PCVAD||↑survival||Messier et al.||2007|
|Pigs||PCVAD||↑ADG, ↓clinical symptoms||Morés et al.||2007|
|Calves||Coronavirus||↑recovery||Arthington et al.||2002|
|Calves||Crypto. parvum||↓scours, ↓shedding||Hunt et al.||2002|
|Calves||E. coli||↑survival, ↑ADG, ↓scours||Nollet et al||1999b|
|Calves||E. coli||↑survival, ↑ADG, ↓scours||Quigley and Drew||2000|
|Shrimp||White Spot Syn. Virus||↑survival, ↑ADG||Russell & Campbell||2000|
|Trout||Yersinia ruckeri||↑survival, ↑ADG||Aljaro et al.||1998|
|Poults||Pasteurella multocida||↑survival, ↑ADG||Campbell et al.||2004b|
APC Inc., Ankeny, IA
Oral Presentation by: H.D. Tyler
Iowa State University, Ames, IA