Invited Paper: Nutritional and management considerations for beef cattle experiencing stress-induced inflammation 1

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1 The Professional Animal Scientist 33: American Registry of Professional Animal Scientists. All rights reserved. Invited Paper: Nutritional and management considerations for beef cattle experiencing stress-induced inflammation 1 R. F. Cooke 2 Eastern Oregon Agricultural Research Center, Oregon State University, Burns ABSTRACT Beef cattle are exposed to several stressors when relocated from cow-calf ranches to feedlots, including transport and feedlot entry. These events elicit a myriad of stressors that increase (P < 0.05) plasma concentrations of proinflammatory cytokines and acute-phase proteins (APP), and the magnitude of the APP response during feedlot receiving was negatively correlated (r = 0.50, P < 0.01) with ADG and DMI. Hence, strategies to decrease the stress-induced APP response during feedlot receiving were investigated. In Exp. 1, steers were assigned to continuous road transport for 1,290 km, or road transport for 1,290 km with rest stops every 430 km. Inclusion of rest stops decreased (P 0.04) plasma APP concentrations on d 1 of feedlot receiving but did not increase receiving (P > 0.68) ADG and G:F. In Exp. 2, steers received or not Ca-soaps of soybean oil during a 28-d preconditioning and then were transported for 24 h. Supplemented steers had less (P < 0.01) plasma concentrations of tumor necrosis factor-α and greater (P = 0.02) ADG during feedlot receiving. In Exp. 3 and 4, respectively, steers were transported and administered flunixin meglumine at truck loading and unloading (1,280-km transport) or meloxicam at loading and during the initial 7 d of receiving (1,440-km transport). Both treatments decreased (P < 0.05) the APP response during feedlot receiving, but only meloxicam increased (P < 0.04) receiving ADG and G:F. Therefore, inclusion of rest stops during transport, supplementing essential fatty acids during preconditioning, and administering nonsteroidal anti-inflammatory drugs are methods to decrease the stress-induced APP response during feedlot receiving, whereas essential fatty acids and meloxicam enhanced receiving performance. Key words: beef cattle, inflammation, management, nutrition, stress 1 This article was based on a presentation at the ARPAS Symposium Understanding Inflammation and Inflammatory Biomarkers to Improve Animal Performance at the 2016 Joint Annual Meeting, July 19 23, 2016, Salt Lake City, Utah. 2 Corresponding author: reinaldo.cooke@oregonstate.edu INTRODUCTION Stress response is commonly defined as the sum of all reactions of an individual to factors that potentially influence its homeostasis (Moberg, 2000). The foundation for this concept emerged more than 70 yr ago, when stress was first employed in the medical community by Hans Selye, who also proposed that an organism responds similarly to different types of stressors in an effort to maintain homeostasis (Selye, 1973). Although the physiologic consequences of stress are still not fully elucidated (Pacak and Palkovits, 2001), it has been demonstrated that stressors affect the immune system, as well as different responses within the body, mainly via the hypothalamic-pituitaryadrenal (HPA) axis and the sympathetic nervous system (Elenkov et al., 2000). Beef cattle are inevitably exposed to stress during their productive lives (Carroll and Forsberg, 2007). These include psychologic, physiologic, and physical stressors associated with management procedures currently practiced within beef production systems. A classic example occurs during transfer of beef calves from cow-calf ranches to commercial feedlots, when cattle are exposed to several stressors within a short period of time (Araujo et al., 2010). These include weaning, commingling with different animals, and exposure to novel environments (psychologic stressors), injury, thermal stress, fatigue, feed and water deprivation during road transport (physical stress), as well as the resultant disruption in endocrine or neuroendocrine function (physiologic stress) characterized by activation of the HPA axis (Carroll and Forsberg, 2007). The combination of some or all of the aforementioned stressors has been shown to directly decrease cattle performance and increase risk to bovine respiratory disease complex (Duff and Galyean, 2007). This complex, often composed of viral, bacterial, and mycoplasmal infections (Ellis, 2001), is the most common and costly disease of feedlot cattle in the United States (NASS, 2006). Such economical losses include, besides cattle mortality, costs associated with wasted feed resources, purchase of pharmaceuticals, and decreased performance of morbid cattle (Loerch and Fluharty, 1999). Hence, strategies that prevent stress-related health disorders elicited by routine cattle management procedures are warranted to promote beef cattle welfare and productivity.

2 2 Cooke STRESS AND THE INNATE IMMUNE SYSTEM Elevated cortisol is one of the main outcomes of the HPA activation, independent of whether the stressor is from psychological, physiological, or physical nature (Crookshank et al., 1979; de Kloet et al., 2005; Carroll et al., 2009). This is the reason why cortisol is generally considered the paramount to the neuroendocrine stress response (Sapolsky et al., 2000) and also a major link between stress and immune function (Glaser and Kiecolt-Glaser, 2005). During episodes of chronic stress, sustained increases in circulating cortisol promote an anti-inflammatory and immunosuppressive response, mainly by decreasing synthesis of proinflammatory cytokines by immune cells (Kelley, 1988). Conversely, sharp increases in circulating cortisol, such as during acute stress, have been shown to elicit a temporary immune response, more specifically an inflammatory reaction. Our research group was the first to report transient increases in proinflammatory cytokines in overtly healthy beef cattle during feedlot receiving (Cooke et al., 2011b), as well as in beef cattle receiving i.v. infusion of corticotrophin-release hormone as a model to stimulate the HPA axis (Cooke et al., 2012b). These results indicate that, besides their recognized immunosuppressive potential, stressors can also activate the innate immune Figure 1. Plasma cortisol (ng/ml), serum nonesterified fatty acids (NEFA; μeq/l), and plasma ceruloplasmin (mg/dl) concentrations during a 28-d feedlot receiving period in cattle subjected to 24-h transport for 1,200 km (TRANS), no transport but feed and water deprivation for 24 h (RSTR), or no transport and full access to feed and water (CON). Treatments were concurrently applied from d 0 to 1. Within days, letters indicate the following treatment differences (P 0.05): a = TRANS vs. CON, b = RSTR vs. CON, c = TRANS vs. RSTR. Error bars indicate SE. Adapted from Marques et al. (2012).

3 Stress-induced inflammation in beef cattle 3 response in animals without the presence of a pathogen. Further, this response is characterized by proinflammatory cytokines, which in turn elicit a major component of innate immune system: the acute-phase response (Murata et al., 2004). Accordingly, our and other research groups also demonstrated that both corticotrophin-release hormone challenge and stress resultant from feedlot entry culminate in increased circulating concentrations of acutephase proteins (APP) in cattle, particularly haptoglobin and ceruloplasmin (Arthington et al., 2005; Arthington et al., 2008; Cooke et al., 2011b, 2012b). Although both proinflammatory cytokine and APP responses are imperative components of the innate immune system and indispensable for early homeostatic restoration following pathogenic infection (Kushner, 1982), these reactions may be unnecessary when induced by stressors and have detrimental effects on health parameters by contributing toward a subsequent immunosuppressive state. Circulating levels of cytokines and APP were positively linked with the incidence of various diseases and certain cancers in humans and animals (Young et al., 1996; Harris et al., 1999) including the bovine respiratory disease complex in feedlot cattle (Berry et al., 2004), although it is still unknown whether the nature of such relationships was based on cause or effect. Alternatively, it is well known that both proinflammatory and APP responses demand a significant amount of body resources, increase maintenance requirements, and decrease nutrient intake (Elsasser et al., 1997; Johnson, 1997). Indeed, research from our group reported a negative correlation (r 0.50; Araujo et al., 2010) between circulating concentrations of APP with DMI and ADG in receiving cattle, indicating that this stress-induced response is also detrimental to animal productivity. Collectively, these results suggest that the stress-induced proinflammatory and APP responses expend a significant amount of biological resources required to maintain robust innate and adaptive immune systems, which increases the susceptibility of the animal to diseases. Nevertheless, research is warranted to validate this theory and further understand the complex association between acute and chronic stress with innate and adaptive immunity. STRESS INDUCED BY CATTLE MANAGEMENT As mentioned previously, road transport and feedlot entry elicit a myriad of stressors in cattle, which in turn have been shown to stimulate inflammatory and APP responses (Araujo et al., 2010; Cooke et al., 2011b; Francisco et al., 2012). Examples of such stressors include nutrient deprivation, physical injury, and strenuous exercise (Swanson and Morrow-Tesch, 2001). This is of particular importance to beef systems where long transport from cow-calf and backgrounding operations to feedlots are inevitable. To better understand one of the several stressors associated with road transport, our research group evaluated the role of feed and water restriction, which are unavoidable during Table 1. Feedlot receiving performance of transported feeder cattle subjected to different management and nutritional interventions Item BW shrink 1 (%) ADG (kg/d) DMI (kg/d) G:F (g/kg) Marques et al. (2012) 2 CON 0.07 a 1.27 a a RSTR 8.1 b 0.97 b ab TRANS 9.6 c 0.91 b b SEM P-value <0.01 < Cooke et al. (2013a) 3 CON 1.25 a 1.28 a a STOP 5.82 b 1.09 b b CTRSP c 1.13 b ab SEM P-value < a c Within columns and study, values with different superscripts differ (P < 0.05). 1 Based on BW loss from truck loading to feedlot arrival (24-h transport). 2 Cattle were subjected to transport for 24 h for approximately 1,200 km (TRANS), no transport but feed and water deprivation for 24 h (RSTR), or no transport and full access to feed and water (CON), and then assigned to a 28-d feedlot receiving period. 3 Cattle were subjected to continuous road transport for 1,290 km (CTRSP), road transport for 1,290 km but with rest stops every 430 km (STOP), or no transport and full access to feed and water (CON), and then assigned to a 28-d feedlot receiving period. During each rest stop, STOP cattle had ad libitum access to alfalfa-grass hay and water for 2 h before being reloaded into the same commercial livestock trailer.

4 4 Cooke road transport, to the welfare and performance challenges experienced by receiving cattle (Marques et al., 2012). Nutrient deprivation stimulates mobilization of body fat reserves and stimulated the HPA axis (Ward et al., 1992; Henricks et al., 1994; Cooke et al., 2007), which are known to trigger an APP reaction in cattle (Cooke and Bohnert, 2011; Cooke et al., 2012b). Feed and water deprivation may also disrupt the ruminal ecosystem and cause microbial death (Meiske et al., 1958), resulting in the release of microbial endotoxins that also elicit an APP response (Carroll et al., 2009). Therefore, Marques et al. (2012) compared the effects of 24-h road transport (1,200 km) or 24-h feed and water deprivation (without transport) on physiological and performance responses of feeder cattle. Interestingly, 24-h road transport and 24-h feed and water deprivation stimulated breakdown of fat reserves, elicited neuroendocrine and APP responses (Figure 1), and similarly decreased cattle performance (Table 1). These results helped elucidate some of the mechanisms responsible for the APP reaction experienced by transported cattle, which has been negatively associated with health and productivity during feedlot receiving (Berry et al., 2004; Qiu et al., 2007; Araujo et al., 2010). Over the last years, our group also demonstrated that cattle with excitable temperament have decreased reproductive performance compared with cattle with adequate temperament (Cooke et al., 2009; Cooke et al., 2011a, 2012a). It is also known that cattle with excitable temperament have decreased feedlot performance than calmer cohorts (Nkrumah et al., 2007; Hoppe et al., 2010). Given that excitable temperament is also a stress response associated with the HPA axis (Cooke, 2014), we speculated that excitable cattle had a heightened APP response when transported to feedlots, resulting in decreased receiving Figure 2. Plasma haptoglobin (μg/ml) and ceruloplasmin (mg/dl) concentrations during a 28-d feedlot receiving period of beef steers classified on d 0 (before 1,380-km road transport) as adequate or excitable temperament (Cooke, 2014). Treatment comparison: P = 0.07, *P 0.05, **P < Error bars indicate SE. Adapted from Francisco et al. (2012).

5 Stress-induced inflammation in beef cattle 5 performance compared with calmer cattle. To address this rationale, Francisco et al. (2012) evaluated beef steers for temperament at the time of truck loading by chute score and exit velocity, as fully described by Cooke (2014). Steer temperament was classified according to temperament score as adequate ( 3, adequate temperament) or excitable (>3, excitable temperament). Steers were transported for 24 h (1,380 km) and assigned to a 28-d receiving period. As speculated, excitable steers had greater plasma haptoglobin and ceruloplasmin responses (Figure 2) as well as lower ADG than cohorts with adequate temperament during a 28-d feedlot receiving period (1.10 vs kg/d, respectively, SEM = 0.05). These results clarify some of the reasons why excitable cattle have lower feedlot productivity and provide additional information in regard to strategies that decrease stress-induced APP reactions elicited during transport to feedlot, such as selection of feeder cattle for adequate temperament. STRATEGIES TO DECREASE STRESS- INDUCED INFLAMMATION Based on the previous discussion, several strategies to decrease the stress-induced APP response during feedlot receiving were investigated by our research group, including administration of anti-inflammatory agents and rest stops during a long transportation period. Nevertheless, these strategies were evaluated in cattle assigned to a preconditioning program after weaning, which is a key management strategy known to benefit welfare and performance of receiving cattle (Duff and Galyean, 2007). More specifically, the stress caused by weaning is a major stimulus to the HPA axis, as well as inflammatory and APP reactions in beef calves (Arthington et al., 2005). Hence, weaning calves for at least 30 d before transport to feedlot has been shown to benefit their ability in coping with the additional stressors associated with transport and feedlot entry, resulting in decreased APP response and enhanced performance during feedlot receiving (Arthington et al., 2008). In addition, preconditioning programs give the opportunity for incorporation of nutritional and management interventions at the cow-calf ranch, better preparing feeder cattle for the immune challenges associated with transport and feedlot entry (Roeber et al., 2001; Duff and Galyean, 2007; Arthington et al., 2008). Rest Stops During Road Transport To address the negative effects of feed and water deprivation during transport (Marques et al., 2012), Cooke et al. (2013b) compared performance, physiological responses, and APP reactions of feeder cattle weaned and Figure 3. Plasma cortisol (ng/ml), serum nonesterified fatty acids (NEFA; μeq/l), and plasma haptoglobin (μg/ml) concentrations in cattle subjected to continuous road transport for 1,290 km (CTRSP), road transport for 1,290 km but with rest stops every 430 km (STOP), or no transport and full access to feed and water (CON), and then assigned to a 28-d feedlot receiving period. During each rest stop, STOP cattle had ad libitum access to alfalfa-grass hay and water for 2 h before being reloaded into the same commercial livestock trailer. Values obtained before treatment application (d 0) served as a covariate. Within days, letters indicate the following treatment differences (P 0.05): a = CTRSP vs. CON, b = CTRSP vs. STOP, c = STOP vs. CON. Error bars indicate SE. Adapted from Cooke et al. (2013b).

6 6 Cooke Figure 4. Plasma concentrations of tumor necrosis factor-α (TNFα; μg/ml) and fatty acids (mg/g of freeze-dried plasma) of beef steers offered preconditioning diets without (CON) or with the inclusion of Ca-soaps of soybean oil (SUPP) from d 28 to 0 relative to transport (d 0) and feedlot entry (d 1). Treatment comparison: *P 0.05, **P < Error bars indicate SE. Adapted from Cooke et al. (2011b). preconditioned for 45 d before road transport but assigned to (1) no transport and full access to feed and water; (2) continuous road transport for 1,290 km; or (3) road transport for 1,290 km with rest stops every 430 km, resulting in a total of 2 rest stops of 2 h each when cattle had ad libitum access to hay and water. The adoption of rest stops Table 2. Preconditioning and receiving performance responses of steers offered preconditioning diets without (CON) or with the inclusion of EFA (SUPP) Item CON SUPP SEM P-value Cooke et al. (2011a) 1 Preconditioning variables (d 28 to 0) Preconditioning ADG, kg/d Preconditioning DMI, %BW Preconditioning G:F, g/kg Feedlot variables Receiving ADG (d 1 to 144), kg/d Finishing ADG (d 145 to 252), kg/d Carcass traits 2 Marbling YG % Choice Cappellozza et al. (2012) 3 Preconditioning variables (d 28 to 0) Preconditioning ADG, kg/d Preconditioning DMI, %BW <0.01 Preconditioning G:F, g/kg Feedlot variables (d 1 to 29) Receiving ADG, kg/d Receiving DMI, kg/d <0.01 Receiving G:F, g/kg Beef steers were offered preconditioning diets with (SUPP) or without (CON) the inclusion of Ca-soaps of soybean oil (150 g/steer daily) from d 28 to 0 relative to transport (d 0) and feedlot entry (d 1). 2 Marbling score: 400 = Small 00, 500 = Modest 00. Yield grade calculated as reported by Lawrence et al. (2010). 3 Beef steers were offered preconditioning diets without or with the inclusion of camelina meal (0.62 kg of DM/steer daily) from d 28 to 0 relative to transport (d 0) and feedlot entry (d 1).

7 Stress-induced inflammation in beef cattle 7 did decrease BW shrink (Table 1), as well as the cortisol, nonesterified fatty acids, and APP responses elicited by road transport and feedlot entry (Figure 3). However, no benefits were detected in ADG, DMI, or G:F (Table 1). Additional research is warranted to further investigate the proper length and subsequent benefits of rest stops during road transport, while taking into account the challenges associated with transport logistic, biosecurity, and animal welfare due to the stress associated with loading and unloading. Nevertheless, results from Cooke et al. (2013b) suggest that rest stops may be a method to reduce the stress-induced APP response during feedlot receiving. Supplementing EFA During a Preconditioning Program Our research group also evaluated whether supplementing beef steers with EFA sources during a preconditioning program would modulate receiving performance and APP responses (Cooke et al., 2011b; Cappellozza et al., 2012). More specifically, EFA are known to have nutraceutical effects (Hess et al., 2008) and modulate the immune system via synthesis of eicosanoids and cytokines (Miles and Calder, 1998). The reason steers received EFA supplementation only during preconditioning in these studies is that EFA inclusion into receiving diets has been shown to decrease cattle DMI and subsequent ADG (Araujo et al., 2010). Cooke et al. (2011b) supplemented beef steers with (SUPP) or without (CON) Ca soaps of soybean oil during a 28-d preconditioning program. After preconditioning, steers were transported for 1,300 km to a commercial feedlot where they remained as a single group until slaughter. During preconditioning, ADG and G:F were similar between SUPP and CON, whereas DMI was decreased in SUPP steers (Table 2). Plasma concentrations of linoleic acid and PUFA were greater in SUPP steers at the time of transport to feedlot, whereas plasma concentration of tumor necrosis factor-α were greater in CON than SUPP steers 3 d after feedlot arrival (Figure 4). During feed- Figure 5. Plasma concentrations of haptoglobin (μg/ml) and ceruloplasmin (mg/dl) in beef steers transported 1,280 km and administered flunixin meglumine (FM; 1.1 mg/kg of BW, i.v.) or 0.9% saline (NOFM; ml/kg of BW, i.v.) at loading (d 0) and upon arrival (d 1), or nontransported steers administered 0.9% saline (CON; ml/kg of BW, i.v.). Treatments were concurrently applied on d 0 and 1. Values obtained before treatment application (d 0) served as a covariate. Within days, letters indicate the following treatment differences (P 0.05): a = NOFM vs. CON, b = FM vs. CON, c = NOFM vs. FM. Error bars indicate SE. Adapted from Cooke et al. (2013a).

8 8 Cooke lot receiving, SUPP had greater ADG than CON but not during the finishing phase (Table 2). Nevertheless, carcass marbling upon slaughter were greater for SUPP than CON steers (Table 2). Cappellozza et al. (2012) evaluated the inclusion of camelina meal in a research design similar to that of Cooke et al. (2011b). During the 28-d preconditioning period, DMI and ADG were lower in SUPP than CON steers, but no differences were detected for G:F (Table 2). During a 28-d feedlot receiving period, SUPP and CON steers had similar ADG and DMI, whereas SUPP had greater G:F than CON steers (Table 2). Collectively, results described by Cooke et al. (2011b) and Cappellozza et al. (2012) indicate that EFA supplementation during preconditioning appears to be a nutritional method that benefits immunological and performance parameters of feeder cattle during feedlot receiving. Further, supplementing Ca soaps of soybean oil resulted in additional benefits on carcass quality, whereas carcass parameters were not evaluated when camelina meal was supplemented by Cappellozza et al. (2012). Nonsteroidal Anti-Inflammatory Drugs (NSAID) Our group also investigated whether administering NSAID to cattle before transport and upon feedlot entry, including flunixin meglumine (Banamine; Merck Animal Health, Summit, NJ) or meloxicam (Carlsbad Technologies Inc., Carlsbad, CA), would benefit receiving performance and immunological parameters without the need for specific preconditioning diets and management. Cooke et al. (2013a) evaluated physiological and performance responses of feeder cattle weaned and preconditioned for 35 d before road transport, which were assigned to (1) transport for 1,280 km in a commercial livestock trailer and administration of flunixin meglumine (1.1 mg/ kg of BW; i.v.) at loading (d 0) and unloading (d 1); (2) transport for 1,280 km in a commercial livestock trailer and administration of 0.9% saline (0.022 ml/kg of BW; i.v.) at loading (d 0) and unloading (d 1); or (3) no transport and administration of 0.9% saline (0.022 ml/kg of BW; i.v.) concurrently with loading (d 0) and unloading (d 1) of flunixin meglumine and transport cohorts. Administration of flunixin meglumine decreased plasma concentrations of ceruloplasmin and haptoglobin during the initial days of a 28-d feedlot receiving period (Figure 5) but did not benefit receiving ADG, DMI, or G:F (Table 3). Guarnieri Filho et al. (2014) evaluated the oral administration of meloxicam in a research design similar to Cooke et al. (2013a). More specifically, steers were assigned to (1) road transport for 1,400 km and daily administration of meloxicam (1 mg/kg of BW daily) from d 0 to 7, (2) road transport for 1,400 km and daily administration of lactose monohydrate (1 mg/kg of BW daily; a pharmacologically inactive excipient used in the manufacture of meloxicam tablets) from d 0 to 7, or (3) no transport and daily administration of lactose monohydrate (1 mg/kg of BW dai- Table 3. Feedlot receiving performance of beef steers receiving nonsteroidal anti-inflammatory drugs before transport and upon feedlot entry Item BW shrink 1 (%) ADG (kg/d) DMI (kg/d) G:F (g/kg) Cooke et al. (2013b) 2 CON 0.46 a 1.18 a a FM 8.85 b 0.99 b b NOFM 8.89 b 1.02 b ab SEM P-value < Guarnieri Filho et al. (2014) 3 CON 0.71 a 1.50 a a MEL 9.07 b 1.48 a a NOMEL 9.83 b 1.26 b b SEM P-value < a,b Within columns and study, values with different superscripts differ (P < 0.05). 1 Based on BW loss from truck loading to feedlot arrival (24-h transport). 2 Beef steers were transported 1,280 km and administered flunixin meglumine (FM; 1.1 mg/kg of BW, i.v.) or 0.9% saline (NOFM; ml/kg of BW, i.v.) at loading (d 0) and upon arrival (d 1), or nontransported steers were administered 0.9% saline (CON; ml/kg of BW, i.v.) concurrently with FM and NOFM administration. From d 1 to 28, steers were assigned to a 28-d feedlot receiving period. 3 Beef steers were transported 1,440 km and received meloxicam (MEL; 1 mg/kg of BW daily) or lactose monohydrate (NOMEL; 1 mg/kg of BW daily) at loading (d 0), unloading (d 1), and daily from d 2 to 7 of feedlot receiving, or nontransported steers concurrently received lactose monohydrate (CON; 1 mg/kg of BW daily). All treatments were administered orally. From d 1 to 28, steers were assigned to a 28-d feedlot receiving period.

9 Stress-induced inflammation in beef cattle 9 ly) from d 0 to 7. Treatments were administered to steers on d 0 and 1 via oral drench, and mixed with the dietary concentrate from d 2 to 7 of feedlot receiving. Meloxicam administration also decreased plasma concentrations of ceruloplasmin and haptoglobin (Figure 6) and prevented the decrease in ADG and feed efficiency observed in transported cattle during feedlot receiving (Table 3). Based on the results described by Cooke et al. (2013a) and Guarnieri Filho et al. (2014), both flunixin meglumine and meloxicam decreased the APP response elicited by road transport and feedlot entry. However, only meloxicam administration benefited receiving ADG and G:F; hence, it seems a feasible method to modulate stresselicited inflammatory reactions and benefit performance of receiving cattle. CONCLUSIONS AND IMPLICATIONS Research has shown that stressors associated with transporting beef cattle from the ranch of origin to feedlots stimulate inflammatory and APP reactions that are detrimental to performance and health of cattle during feedlot receiving (Carroll et al., 2009; Araujo et al., 2010; Cooke et al., 2011b). Our group also reported that nutrient restriction is a major contributor to the APP response and decreased feedlot receiving performance detected in cattle transported for long distances (Marques et al., 2012), whereas these outcomes might be aggravated in cattle with excitable temperament (Francisco et al., 2012). Based on this knowledge, our research group investigated several management strategies to decrease the stress-induced APP responses during feedlot receiving. Inclusion of rest stops during transport (Cooke et al., 2013b), preconditioning EFA supplementation (Cooke et al., 2011b; Cappellozza et al., 2012), and NSAID administration (Cooke et al., 2013a; Guarnieri Filho et al., 2014) are methods to decrease the stress-induced APP response during feedlot receiving, whereas EFA and meloxicam administration enhanced cattle receiving performance (Cooke et al., 2011b; Guarnieri Filho et al., 2014). Nevertheless, the adoption of one or more of the aforementioned methods will depend on the management scheme of the operation, but they are expected to enhance health, production efficiency, and cattle welfare within beef production systems. Figure 6. Plasma concentrations of haptoglobin (μg/ml) and ceruloplasmin (mg/dl) in beef steers transported 1,440 km and that received meloxicam (MEL; 1 mg/kg of BW daily) or lactose monohydrate (NOMEL; 1 mg/kg of BW daily) at loading (d 0), unloading (d 1), and daily from d 2 to 7 of feedlot receiving, or nontransported steers that concurrently received lactose monohydrate (CON; 1 mg/kg of BW daily). Values obtained before treatment application (d 0) served as a covariate. Within days, letters indicate the following treatment differences (P 0.05): a = NOMEL vs. CON, b = NOMEL vs. MEL, c = MEL vs. CON. Error bars indicate SE. Adapted from Guarnieri Filho et al. (2014).

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