Unlocking Solutions to Chronic Inflammation

Transcription

1 to Chronic Inflmmtion Why Feeding Zinpro Performnce Minerls is Key For Success When Formulting Diets for Livestock, Poultry, Aquculture, Equine nd Compnion Animls By Adm Geiger, Ph.D., diry reserch nutritionist, Mrco Reollo, DVM, poultry reserch specilist nd Mrk Wilson, Ph.D., swine reproductive physiologist, Zinpro Corportion Inflmmtion is nturl nd essentil component of the immune response to infection, pthogens nd/or tissue dmge. While often considered negtive rection, inflmmtion serves s protective response to pthogens or tissue dmge. It lso promotes lood flow nd immune cell recruitment to the insult site, which ssists the niml in eliminting the initil cuse of injury nd promotes ffected tissue recovery. While n pproprite inflmmtory response is necessry, excessive or prolonged inflmmtion cn ecome detrimentl to the niml in mny wys. Animls suffering from chronic, prolonged inflmmtion my e unle to mount successful immune response in the future. Chronic inflmmtion lso pulls nutrients nd energy wy from other key functions within the niml such s growth, reproduction, nd met, milk or egg production. An niml undergoing n inflmmtory response cn esily lose more thn one kilogrm of energy (glucose) to the immune system in dy. This energy could e used for performnce nd production. Bsed on this loss lone, it cn e rgued tht meliorting n inflmmtory response when possile needs to e top priority for niml griculture. Given the recent trend in mny countries to move wy from ntiiotic use, methods to effectively mnge nd minimize inflmmtion re ecoming incresingly importnt. Mny potentil Given the recent trend in mny countries to move wy from ntiiotic use, methods to effectively mnge nd minimize inflmmtion re ecoming incresingly importnt. dietry ingredients, including trce minerls, re now eing promoted s lterntives to ntiiotics in order to enhnce niml wellness nd performnce in poultry, swine, nd diry nd eef cttle. Since inflmmtion is intertwined with the immune response, conditions nd feedstuffs or ingredients tht help modulte the inflmmtory response, nd susequent immune function, re vitl to niml griculture. Trce minerls re essentil to ll living cretures, nd production nimls re no exception. Recent dt hs shown the enefit trce minerls provide to immune responses nd ssocited inflmmtion (Chirse et l., 1994; Percivl et l., 1998; Underwood nd Suttle, 1999; Gylen et l., 1999; Hudson et l., 24; Kellogg et l., 24; Enjlert et l., 26; Jhnin et l., 28; Sicilino-Jones et l., 28; Riee et l., 21). How well diet meets n niml s trce minerl needs will vry y not only the mount of trce minerls consumed, ut lso y trce minerl source, level of ntgonists in the diet nd stress. Feeding Zinpro Performnce Minerls hs een hevily reserched in mny production species. Extensive peer-reviewed reserch hs shown this unique trce minerl ctegory, known s Performnce Trce Minerls, to significntly improve livestock nd poultry wellness nd performnce y minimizing the effects from oth ntgonists nd stress on trce minerl vilility. This review will highlight the role Zinpro Performnce Minerls plys in the immune response nd mitigtion of chronic inflmmtion.

2 Inflmmtion nd the Innte Immune System Inflmmtion nd the Skin The first line of defense ginst thret to immunity is epithelil tissue. Commonly referred to s the lrgest immune orgn, skin ers the constnt urden of protecting ody s internl orgns from dmge nd invding pthogens. In poultry, skin prevents infections nd potentil food-poisoning cteri from entering crcsses. As clssified y food inspectors, cellulitis is considered the second most importnt condemntion cuse in poultry processing plnts in the United Sttes. From n niml wellness nd commercil perspective, mintining skin integrity is criticl mens to prevent numer of normlities, such s cellulitis, tht fflict poultry nd other livestock. Positive improvements to skin integrity nd reduced skin normlities in response to supplementing poultry with n effective zinc source (such s Avil Zn or ZINPRO zinc methionine from Zinpro Performnce Minerls) re commonly oserved. This is no surprise, given the multitude of roles zinc plys in epithelil production, mintinnce nd repir (Mertz, 1986). Specificlly, zinc is known to influence skin strength, elsticity, inflmmtory response nd heling. Zinc from Zinpro Performnce Minerls hs een shown to heighten immunity (s reviewed y Kidd et l., 1996; Moghddm et l., 29, 216) nd reduce the incidence of cellulitis lone or in comintion with vitmin E (Downs et l., 2; Figure 1). In roiler study t Auurn University, skin lesions (sores, scs nd scrtches) decresed from 42.7 percent to 9.6 percent when irds were fed zinc from Zinpro Performnce Minerls (Senmhyk, et l., 21; Figure 2). The severity nd frequency of foot pd dermtitis ws lso reduced in roilers fed zinc from Zinpro Performnce Minerls (Hess et l., 21; Senmhyk et l., 21). The effect of zinc from Zinpro Performnce Minerls on the epithelil inflmmtory response is evident in chickens injected with phytohemgglutinin in the toe we (incresed skin thickness nd lymphocyte prolifertion; Moghddm nd Jhnin, 29) nd wttle (enhnced Figure 1. Effect of Vitmin E nd Avil Zn on the Incidence of Cellulitis Severity And Incidence Of Cellulitis % of Birds Control c Vitmin E Avil-Zn d Vitmin E + Avil-Zn Avil-Zn zinc mino cid complex A derml scrtch procedure ws used to elicit cellulitis c Zinc from zinc sulfte source d Control + 4 ppm zinc from Avil-Zn Downs, et l., 2. J. Appl. Poultry Res. 9: Figure 2. Effects of Avil Zn on 49 Dy Skin Integrity 49 d Skin Integrity z 8 ppm Zn from ZnSO4 Avil-Zn zinc mino cid complex replced 4 ppm Zn from ZnSO4 c Avil-Zn provided 4 ppm Zn on top of ZnSO4 yz Mens lcking common superscript letter differ, P <.5 cutneous sophil hypersensitivity; Kidd, et l., 1993). In ruminnts, the importnce of skin integrity to overll helth is lso well documented. One such re susceptile to invding orgnisms is the skin region ner the hoof horn. Of prticulr interest is the disorder known s digitl dermtitis. Acute (M2) digitl dermtitis typiclly ppers s right-red, ctive lesion on the skin ove the heel ul, nd is cused y host of cteri invding the re when skin integrity is compromised. In prticulr, neroic cteri (Spirochetes), such s Treponem species my enter the compromised skin to cuse excessive inflmmtory response when conditions re not idel (wet, poor hygiene, etc.). Multiple studies Sulfte Avil Zn Iso Avil-Zn c On Top THIGH 9.6 y SORES SCABS SCRATCHES, % 26.3 yz BACK 4. No Lesions Mild Lesions Moderte Lesions Severe Lesions All Lesions 4.4 hve shown tht feeding comintion of zinc, mngnese nd copper s mino cid complexes nd colt s colt glucoheptonte from Zinpro Performnce Minerls to diry nd eef cttle cn limit the impct/occurrence of digitl dermtitis, while lso improving clw integrity nd decresing the incidence of lmeness nd other clw disorders (Gomez et l., 214; Kulow et l., 217). The impct of trce minerls on hoof integrity extends eyond the skin. One primry inititor of the inflmmtory pthwy is vi the toll-like receptors (TLR). The primry outcome of the TLR pthwy is the synthesis of proinflmmtory metolites (De Nrdo et l., 215). In study conducted t the University of Illinois (Osorio et l.,

3 216), cows fed zinc, mngnese nd copper s mino cid complexes nd colt s colt glucoheptonte from Zinpro Performnce Minerls, in plce of sulfte forms, hd greter expression of one of the TLR genes. However, these nimls lso hd decresed expression of genes coding for downstrem metolites in the hoof corium. This reduction in gene expression reflects less inflmmtion in the corium of cows fed Zinpro Performnce Minerls, s well s potentil rediness to respond to n cute insult if necessry. Cows fed Zinpro Performnce Minerls lso hd greter expression of genes tht regulte the ntioxidnt response, which cn hve ovious, positive impcts on n inflmmtory response (Wng et l., 215). Tken s whole, one possile explntion for these oserved results (i.e., reduction in clw disorders, such s digitl dermtitis) is tht cows fed Zinpro Performnce Minerls more effectively initite the eginning stte of n inflmmtory response without inititing the entire inflmmtion pthwy. Insted, there is n oserved decrese in expression of downstrem metolites in cows fed trce minerls from Zinpro Performnce Minerls. This my e due to production of more structurlly sound tissue in these nimls, resulting in less tissue dmge. Inflmmtion nd Vsculr Frgility Vsculr systems often ecome frgile following periods of infection or vrious forms of stress including metolic stress. When hndling irds either efore or during live hul, numer of hemorrhgic lesions cn e produced. Common crcss defects include ruises, lood splsh, rest listers, nd red wing tips (Figure 3). In ddition, vsculr frgility issues cn sometimes e linked to mycotoxins. Inflmmtion due to metolic stress cn ply n importnt role in incresing the severity of hemorrhges. Both cute nd chronic inflmmtion, regrdless of whether it is infectious or non-infectious, influence vsculr integrity nd function y creting endothelil dysfunction, compromising vsculr tone, thromosis nd vsculr remodeling. Oxidtive stress ssocited with inflmmtion cn dysregulte the Figure 3. Exmple of Mild Hemtom (Score 1) Wing Bleeding production of nitric oxide (NO), essentil for the endothelil cells. This leds to the production of superoxide nions nd peroxynitrite (ONOO - ) which ecome very hrmful for the lood vessels. Zinc plys importnt roles in the protection of these cells y incresing nti-oxidnt sttus [zinc-medited glutthione de novo synthesis, incresing superoxide dismutse (SOD) ctivity] nd y down-regulting inducile nitric oxide synthse (inos) derived NO formtion. inos production is instrumentl during the inflmmtory response ut it ecomes hrmful if it is not regulted known s errnt production of NO. Zinc-medited regultion of inos expression is ffected y the regultion of NF-k trnsctivtion. Reserchers in Germny hve een le to reproduce some of these pthwys y exogenous dded zinc. In niml nutrition, numer of poultry studies using Avil-Zn zinc mino cid complex hve shown reduction in the ppernce, severity nd durtion of hemorrhges in poultry crcsses. Reserchers in Colordo, USA, found reduction (38 percent, P <.11) in ruising re (in 2 ) in crcsses coming from 53 d roilers supplemented with 1 ppm zinc (4 ppm from Avil-Zn nd 6 ppm from Figure 4. Effect of Avil Mins on Incidence of Blood Splshes in Crcsses of 49-Dy-Old Broilers % Sulfte Norml Mild Severe P =.6 Avil Zn zinc mino cid complex, Avil Mn mngnese mino cid complex nd Avil Cu copper mino cid complex Zinpro Crcss Lesion Scoring Guide Significnt differences etween tretments were found (P =.6, chi-squre) in the frequency of lesions present on crcsses ZPM Interntionl Inflmmtion Symposium 217

4 zinc sulfte), when compred to roilers fed only zinc sulfte t the sme totl level. In 213, Khttk nd collegues from Scotlnd s Rurl College reported reduction in the severity nd incidence (46 percent, P <.5) of hemtom in wings of crcsses from 35 d roilers fed Avil-Zn compred to those fed zinc sulfte. More recently in 216, Petrcci nd collegues t University of Bologn found reduction in lood splshes (Figure 4; 45 percent, P <.1) in legs nd thighs from 49 d roilers feeding comintion of zinc, mngnese nd copper mino cid complexes (Avil ZMC). These findings confirm the role of zinc in protecting endothelil tissues nd shows the dvntge Avil-Zn zinc mino cid complex sources hve over feeding n inorgnic trce minerl source. I nflmmtion nd the Gstrointestinl Trct The gstrointestinl trct (GIT) is one of the lrgest immune orgns in the ody. When pthogens re ingested nd rech the lumen of the GIT, they hve not yet een sored into the niml s ody. Mintining GIT epithelium integrity is of the utmost importnce to prevent pthogens from invding the ody, similr to tht of the skin. Severl key ntomicl fetures of the intestinl epithelium id its ility to mintin the rrier etween pthogens in the gut lumen nd the internl ody. The mucosl epithelil lyer contins golet cells, which secrete mucous nd mucins tht provide the initil protection lyer over the enterocytes of the intestinl epithelium. In ddition, these enterocytes re stitched together y tight junction complexes (Figure 5). This region is importnt for limiting the mount of hrmful cteri nd contents of the intestinl lumen from entering the lood strem. Dehydrtion, mlnutrition, cold stress, nd oxidtive free rdicls cn ll cuse the epithelil lining to e wekened, potentilly leding to pthogen invsion into the niml s ody. Het stress nd ssocited reduced feed intke cn lso decrese intestinl integrity nd increse circulting endotoxins in production nimls (Perce et l., 213, 214). Replcing inorgnic zinc with zinc from Zinpro Performnce Minerls Tight Junction Complex Figure 5. Protein Stiching of the Tight Junctions Between Two Enterocytes JAM1 Actin cytoskeleton ZO3 ZO1 JAM1 Cludin ZO2 ZO1 ZO2 ZO3 Occludin JAM1 JAM1 Villi Zinc plys n importnt role in mintining the physiologicl function of the gstrointestinl trct (Alm et l., 1994). m SwGr - 22 hs een shown to mitigte potentil gut lekge in pigs ssocited with cute nd chronic het stress (Perce et l., 215; Myorg, et l., 217). Improved gut integrity resulted in decresed presence of TNFα in lood, suggesting tht zinc from Zinpro Performnce Minerls cn help prevent some of the endotoxin s negtive effects y reducing the mount of endotoxins tht enter circultion. In ddition, the gut morphology of pigs fed zinc from Zinpro Performnce Minerls ws more similr to pigs housed under therml-neutrl conditions (Figure 6). Similr to wht ws oserved in hetstressed pigs, feeding zinc from Zinpro Performnce Minerls helped mintin intestinl morphology/integrity of hetstressed steers in mnner similr to steers housed under therml-neutrl conditions (Figure 6; Aujmeh et l., 216). In this study, feeding zinc from Zinpro Performnce Minerls in plce of inorgnic zinc improved het tolernce Figure 6. Comprison of Swine nd Ruminnt Intestinl Morphology Providing zinc from Zinpro Performnce Minerls improves intestinl morphology/integrity compred to tht of non-het-stressed nimls fed the control diet. Key: Intestinl morphology imges for swine re shown in red nd ruminnt re shown in lue. Upper left, therml-neutrl control nimls; Upper right, therml-neutrl pir-fed nimls (reduced feed intke); Lower left, het-stressed nimls with no zinc from Zinpro Performnce Minerls supplementtion; Lower right, het-stressed nimls fed 4 ppm zinc from Zinpro Performnce Minerls.

5 Figure 7. Prevlence of Conjunctivitis, Nsl Dischrge nd Coughing in Broilers Directly Infected with IBV % Prevlence 6% 4% 2% % 29 y 46 z of steers, s evidenced y incresed dry mtter intke nd decresed rectl tempertures. The ility to sor nutrients from the gut my hve een improved for steers fed zinc from Zinpro Performnce Minerls, s these ninls hd decresed duodenl villi width nd incresed jejunum villi height nd height:crypt depth, s compred with hetstressed steers fed only inorgnic zinc. Wening presents nother potentil stressor for lmost every mmmlin species. Dt in piglets indictes tht feeding Zinpro Performnce Minerls hs positive impct on villi ntomy nd incresed numer of golet cells in pigs. Gstric nutrient-intution of piglets 56 z Sulfte Avil-Zn ISO Avil-Zn High Chllenge with Arknss DPI p1 strin of IBV (13.5/EID5/.1mL) y eye-drop t 1 dys of ge Sulfte, 8 ppm supplementl Zn from sulfte; Avil-Zn Iso, 8 ppm supplementl Zn: 4 ppm from sulfte nd 4 ppm from Avil-Zn zinc mino cid complex; Avil-Zn High, 1 ppm supplementl Zn: 4 ppm from sulfte nd 6 ppm from Avil-Zn yz Mens lcking common superscript letter differ, P <.5 Figure 8. Incidence of Airscculitis in Broilers Directly Infected with IBV t 1 Dys Post-Chllenge At 1 d Post-Chllenge Incidence, % z 1 yz y Sulfte Avil-Zn Iso Avil-Zn High Chllenge with Arknss DPI p1 strin of IBV (13.5/EID5/.1mL) t 1 d of ge y eye-drop Sulfte, 8 ppm supplementl Zn from sulfte; Avil-Zn Iso, 8 ppm supplementl Zn: 4 ppm from sulfte nd 4 ppm from Avil-Zn zinc mino cid complex; Avil-Zn High, 1 ppm supplementl Zn: 4 ppm from sulfte nd 6 ppm from Avil-Zn yz Mens lcking common superscript letter differ, P <.5 t irth, d 1, nd d 21, with 4 mg of zinc from Zinpro Performnce Minerls incresed the numer of epithelil golet cells of the jejunul villi nd tended to increse mucosl thickness (Metzler- Zeeli et l., 21). Inflmmtion nd the Respirtory Trct Zinc ppers to hve n importnt role in the integrity nd defense mechnisms of the respirtory epithelium (ntioxidnt, orgnelle stilizer, nti-poptotic gent, epithelil heling nd renewl, nti-inflmmtory; Truong-Trn et l., 2). A study in rits hs shown tht n nticteril peptide with zinc s cofctor is le to reduce E. coli colony counts y 7 percent in the respirtory trct (LForce et l., 1984). A study mesuring intrcellulr zinc in pulmonry rteril endothelil cells showed zinc ws importnt in the reduction of LPS-induced poptosis (Thmiyy, 212). Respirtory trcts of irds re exposed to numer of irritnts. Recent work in chickens chllenged introculrly with pthogenic strin of Infectious Bronchitis Virus (Arknss DPI p1) showed roilers fed zinc from Zinpro Performnce Minerls hd n increse in erly clinicl inflmmtory mnifesttions (Figure 7), nd significntly lower irscculitis (Figure 8). Also oserved were decrese in virus shedding nd irds tht were le to mintin etter dily weight gin 1 dys post-chllenge, compred with zinc sulfte-fed irds (Reollo, unpulished). According to these findings, improved zinc sttus my crete more consistent epithelil rection in the upper respirtory trct, reducing the ccess of hrmful gents to the ir scs, nd in turn, decrese virl output. While some dt exists indicting the role Zinpro Performnce Minerls ply in the respirtory trct of poultry, dt regrding its impct on the respirtory epithelium in mmmls re limited. Anlysis of eef dt indictes tht clves orn to cows fed Zinpro Performnce Minerls hd greter thn 5 percent decrese in tretments for ovine respirtory disese during the growing phse, which contriuted to greter return on investment for those nimls (Mrques et l., 216). Reserch regrding the impct of Zinpro Performnce Minerls on the respirtory epithelium of ruminnts presents gret reserch opportunity. Inflmmtion nd the Reproductive Trct Follow the irthing process, drmtic physiologicl shift occurs in nimls. One such shift occurs in the epithelium of the reproductive trct. It is criticl for production nimls to mount n effective immune response in order to effectively eliminte reproductive trct pthogens tht enter during the irthing process nd to repir tissues dmged during irthing. This helps prepre the niml for susequent pregnncies. Anlysis of endometril gene expression indictes tht Interntionl Inflmmtion Symposium 217

6 Figure 9. Impct of Zinpro Performnce Minerls on Pregnncy Rte of Cows with or without Trnsition Disese % Pregnnt Cows fed Zinpro Performnce Minerls (Zn, Mn, nd Cu mino cid complexes nd Co-glucoheptonte) ecme pregnnt t rte similr to tht of cows tht hd not experienced trnsition disorder. This sme is not true for cows tht were fed only inorgnic trce minerls. cows fed Zinpro Performnce Minerls ttin pro-inflmmtory stte erlier s compred to cows fed only inorgnic minerls (Btistel et l., 217). This my indicte tht cows fed Zinpro Performnce Minerls were le to effectively eliminte pthogens from the reproductive trct nd repir dmged tissue more quickly. This is further confirmed y the differentil expression of other genes known to ply role in eliminting pthogenic cteri tht hve invded the epithelium. However, gene expression dt lone does not necessrily correlte to phenotypic response. A key finding relted to feeding Zinpro Performnce Minerls is the improvement in reproductive performnce ove tht ttined y feeding only inorgnic minerl sources. This ws clerly illustrted in study conducted y Ferguson et l. (24) where feeding Zinpro Performnce Minerls to cows tht experienced trnsition helth disorder, improved reproductive performnce (i.e., pregnncy rtes) to level similr to tht of cows tht never experienced trnsition disorder. The sme results did not occur when only inorgnic trce minerls sources were fed (Figure 9; Ferguson et l., 24). The reproductive process is inherently different in poultry. In irds, egg production nd qulity depends mostly On Pregnncy Rtes Dy Postclving Included retined plcents, metritis, fever, ketosis nd displced omsums Ordinry: zinc sulfte, copper sulfte, mngnese cronte nd colt cronte Ordinry, no trnsition helth disorder 4-Plex c, no trnsition helth disorder Ordinry, trnsition helth disorder 4-Plex, trnsition helth disorder c 4-Plex: ZINPRO zinc methionine, MANPRO mngnese methionine, CuPLEX copper lysine nd COPRO colt glucoheptonte; Tretments fed from 6 d prior to clving through 25 d postprtum Ferguson et l., 24. J. Diry Sci. 87 (Suppl.1):117 (Astr.) on hens hving helthy oviduct. Egg white, shell memrne, shell structure, shell color nd protective cuticle re produced s the egg moves down through the different portions of this orgn. The oviduct is lined with highly specilized cells for ech portion ccording to the egg formtion process. Since zinc, mngnese nd copper re importnt components of the orgnic shell mtrix nd coordinte shell formtion (Yves, 21), dequte levels of these minerls need to e provided t ll times in the feed. Me et l. (23) found tht supplementtion with Zinpro Performnce Minerls improved eggshell qulity in ged lying hens. Guo et l. (22) found n increse in shell glnd cronic nhydrse (zincdependent enzyme tht produces the mjor component of the eggshell) nd n increse in yolk zinc concentrtion of 59- week old lyer hens fed 8 ppm zinc from Zinpro Performnce Minerls, compred to feeding the sme or higher levels of zinc from zinc sulfte. Additionlly, the epithelium in the oviduct is very ctive nd hs continuous turnover. Since some pthogens like Infectious Bronchitis Virus nd Mycoplsm spp. commonly chllenge these cells (Sif, 211), the fortifiction of lyer nd reeder diets with zinc nd mngnese from Zinpro Performnce Minerls could prove helpful due to their known role in immune nd inflmmtory responses. This enefit is n re tht requires dditionl reserch. Inflmmtion nd the Mmmry Glnd In the mmmry glnd, the kertin plug of the tet is one of the first lines of defense to protect the niml from mmmry infection (i.e., mstitis). Feeding zinc from Zinpro Performnce Minerls hs een shown to increse tet kertin production in cows, which my protect the cow from mmmry infection (Jones, 1995). Furthermore, elevted somtic cell counts (SCC) in milk re key indictor of mmmry glnd inflmmtion (Pyörälä, 23), nd numerous studies hve confirmed tht feeding Zinpro Performnce Minerls decreses SCC in lctting diry cttle (Kellogg et l., 23, 24; Sohnird et l., 21; Nyeri et l., 214). A 12-tril summry indicted tht feeding cows zinc from Zinpro Performnce Minerls reduced SCC on verge y nerly 1 (1/mL; Kellogg et l., 24; Figure 1). Anlysis of endometril gene expression indictes tht cows fed Zinpro Performnce Minerls ttin pro-inflmmtory stte erlier s compred to cows fed only inorgnic minerls. Although the ruminnt mmmry glnd is most commonly ssocited with mstitis, severl studies in swine hve shown tht SCC decrese when sows re fed Zinpro Performnce Minerls. A study from the University of Brcelon showed tht feeding sows Zinpro Performnce Minerls in plce of inorgnic trce minerls lowered SCC y roughly 4 (1/mL). A second study hd similr trends, showing n interesting prity response for sows fed zinc from Zinpro

7 Figure 1. The Impct of Zinpro Performnce Minerls on Somtic Cell Count Somtic Cell Count Response, 1s/mL Response To Feeding Zinpro Minerls Somtic cell count is relile indictor of prolonged mmmry glnd inflmmtikon. In summry of 2 studies, Zinpro Performnce Minerls hve een shown to consistently decrese somtic cell count in diry cows. Similr results hve een oserved in swine. Performnce Minerls compred to feeding zinc sulfte. Log trnsformed SCC decresed 2.64 in first prity nd 1.21 in second prity when sows were fed Zinpro Performnce Minerls (Mrtineu et l., 217). Although SCC is relile indictor of inflmmtion within the mmmry glnd, integrity of the mmmry epithelium is lso of prmount importnce. Recent dt indictes tht zinc from Zinpro Performnce Minerls my impct mmmry glnd epithelil integrity. In this study, mid-lcttion cows sujected to either therml-neutrl environments or het-stress conditions were fed 4 ppm zinc from either Zinpro Performnce Minerls or zinc tetrsic chloride (ZnCl). In oth the therml-neutrl nd het-stress phses, plsm lctose incresed in cows receiving only zinc from ZnCl, ut remined unchnged in cows consuming zinc from Zinpro Performnce Minerls. These results indicte tht feeding zinc from Zinpro Performnce Minerls in plce of ZnCl etter mintins mmmry tight junction integrity, which is crucil for milk secretion nd voiding milk lekge from the lumen of lveoli (Weng et l., 216). REDUCTION IN SOMATIC CELL COUNT Supplementtion eginning in the dry period, 3, decrese in SCC AVG Avil 4: Avil Zn zinc mino cid complex, Avil Mn mngnese mino cid complex, Avil Cu copper mino cid complex nd COPRO colt glucoheptonte 4-Plex : ZINPRO zinc methionine, MANPRO mngnese methionine, CuPLEX copper lysine nd COPRO colt glucoheptonte z Tretment effect, P <.15 Kellogg et l., 23. Prof. Anim. Sci. 19:1; Ferguson et l., 24. J. Diry Sci. 87 (Suppl.1):117 (Astr.);Monrdes et l., 22. J. Diry Sci. 85 (Suppl.1):265 (Astr.); Nocek et l., 26. J. Diry Sci. 89:2679; Bllntine et l., 22. Prof. Anim. Sci. 18:211; Uchid et l., 21. Anim. Feed Sci. Technol. 93:193; Toni et l., 27. Prof. Anim. Sci. 23:49; Griffiths et l., 27. Anim. Feed Sci. Technol. 137:69; Sicilino-Jones et l., 28. J. Diry Sci. 91:1985; Hckrt et l., 21. J. Anim. Sci. 88:3856; DeFrin et l., 29. Prof. Anim. Sci. 25:79 Inflmmtion nd the Adptive Immune System -17 z The dptive immune system differs from the innte immune system in the sense tht it hs the ility to recognize specific ntigens nd hs memory function. In contrst, the innte immune system does not hve memory, includes ntomicl fetures tht prevent cteril entry into the ody nd inds to generl clsses of cteril or virl ntigens. Components of the innte immune system include epithelil rriers, mcrophges, grnulocytes, mst cells nd nturl killer cells. Binding to specific peptide sequences would e reserved for the dptive (cquired) immune system components nd their memory-like function. Components of the dptive immune system include B-lymphocytes (1 percent to 2 percent of circulting lymphocyte popultion) nd T- lymphocytes (6 percent to 7 percent of circulting lymphocyte popultion). For simplicity ske, dt from multiple cell clsses will e discussed herein, lthough they my not e specific to the dptive immune system, s mny of these cell types work in concert to mount n inflmmtory event nd successful immune response. A study t the University of Illinois indicted improved helth when trnsition diry cows were supplemented with Zinpro Performnce Minerls (Osorio et l., 216). In this study, feeding Zinpro Performnce Minerls in plce of sulfte forms of zinc, mngnese, copper nd colt, improved liver function, incresed polymorphonucler leukocyte (ttrct leukocytes to site of infection) phgocytosis (greter thn 2 percent), nd incresed ntioxidnt cpcity postprtum. Oxidtive stress cn ctivte vriety of trnscription fctors, which will eventully led to inflmmtion (Reuter et l., 21). While lood totl ntioxidnt cpcity ws lower preclving for cows supplemented with Zinpro Performnce Minerls, postclving these sme cows hd greter totl ntioxidnt cpcity in lood, indicting they were under less oxidtive stress. This my prtilly explin why cows fed Zinpro Performnce Minerls hd reduction in expression of genes for the pro-flmmtory cytokines, such s tumor necrosis fctor nd IL-6. The response oserved in the University of Illinios study mirrors work in finishing steers, where supplementtion with zinc from Zinpro Performnce Minerls positively impcts whole lood white lood cell counts, nd lood eosinophil nd sophil concentrtions (Genther- Schroeder et l., 216). Perhps the most interesting spect of the dt presented from the University of Illinois is the impct of Zinpro Performnce Minerls consumption y the dm on the clf (Jcometo et l., 215). Clves orn to cows supplemented with Zinpro Performnce Minerls during the lst month of gesttion hd decrese in liver dmge nd ltered gene expression, suggestive of more efficient immune system. In contrst, clves orn to cows fed only inorgnic trce minerls hd n upregultion of series of genes tht ultimtely suggested tht those clves were in pro-inflmmtory stte shortly fter irth. This is supported y decrese in rectl tempertures for the first two weeks postprtum in clves orn to dms fed Zinpro Performnce Minerls, potentilly indicting decrese in stress nd inflmmtion following the irthing process. Interntionl Inflmmtion Symposium 217

8 Additionl work in poultry hs shown feeding Zinpro Performnce Minerls to reduce oxidtive stress y lowering MDA (mlondehldehyde), incresing lood uric cid, regulting TLRs nd ntiinflmmtory cytokines, nd incresing polymorphonucleted nd mononucler cell prolifertion nd ctivity (Guo et l., 24; Echeverry et l., 216; Rez et l., 216). As compred to inorgnic sources, feeding Zinpro Performnce Minerls hve shown more consistent effects on the different steps of the inflmmtory response. Zinc nd mngnese from Zinpro Performnce Minerls hve een shown to increse phgocytosis in oth opsonized nd unopsonized turkey lood mcrophges when exposed to sheep red lood cells in vitro (Ferket et l., 1992). This is consistent with studies in mice nd other species where phgocytosis is impired during zinc deficiency nd restored with zinc supplementtion (Drlynn et l., 211; Hmmon et l., 214). Replcing inorgnic zinc nd mngnese with zinc nd mngnese from Zinpro Performnce Minerls incresed tumoricidl ctivity of mcrophges from 25 percent to 65 percent (Ferket et l., 1992). Zinc from Zinpro Performnce Minerls hs lso shown evidence of elevting the sensitivity to LPS (lipopolyscchrides) from Slmonell typhimurium injected in lyer hens, in fever nd circultory cytokine responses (Cheng et l., 24), mening shortened cute phse response. Redistriution of zinc due to inflmmtion ws oserved in LPS-chllenged irds, with incresed zinc sequestrtion in liver nd spleen, nd reduced level in the lood (Cheng et l., 24). This is prt of the inflmmtory response to systemic infections, designed to strve hrmful microorgnisms of zinc nd iron tht re essentil nutrients for mny cteri (Klsing, 1984). Cec IL-1 levels were higher in roilers fed zinc from Zinpro Performnce Minerls fter eing chllenged with E. cervulin, E. mxim nd E. tenell (Troche, 215). Interleukin-1, n importnt nti-inflmmtory cytokine, is produced during chronic infections. It inhiits Th1 cells, NK cells, nd mcrophges nd helps trnsition to M2 phse, turning down excessive response nd eginning tissue repir (Couper et l., 28). This regultory response ws oserved in the previous study when fever nd IL-1 β levels declined fster in irds fed zinc from zinc mino cid complex (Cheng et l., 24). Conclusions Trce minerls re involved in mny enzymes nd processes ssocited with immune system function. Ensuring tht trce minerl requirements re met for production nimls, including poultry, swine, diry nd eef cttle, is criticl in order for the niml to mount n pproprite inflmmtory response. This response egins with the innte immune system, where nimls supplemented with Zinpro Performnce Minerls experience improved skin integrity nd wound heling, enhnced GIT morphology nd integrity, etter mmmry glnd integrity ccompnied y reduction in SCC, nd improved pthogen clering/inflmmtory responses in the reproductive trct following prturition. Moving deeper into the immune system nd the cellulr mechnisms responsile for n inflmmtory response, when production nimls re fed Zinpro Performnce Minerls, n increse in ntioxidnt cpcity is oserved. We lso see n improvement in immune cell function within the lood, which my explin the ility of the niml to neutrlize free rdicls tht cuse oxidtive dmge. In ddition, nimls fed Zinpro Performnce Minerls hve decresed metolites circulting in the lood, which re clssic indictors of pro-inflmmtory stte. The impct of trce minerls on inflmmtion nd the immune system re complex, nd require more detiled nlysis. However, the dt shown here indicte tht feeding Zinpro Performnce Minerls helps improve the inflmmtory stte of production through multiple mechnisms, nd it hs een oserved t the deepest cellulr level, vi the ltertion of key genes ssocited with inflmmtion. The impct of trce minerls from Zinpro Performnce Minerls on production nimls is not limited to the current genertion, ut is lso communicted to the next genertion vi fetl progrmming mechnism tht equips the immune system of the offspring to mount n inflmmtory response when needed. Rememer tht inflmmtory signling is mens of communiction within nimls, nd is criticl to fighting off pthogens nd infections. When Zinpro Performnce Minerls re fed, tht communiction ppers to e improved nd the inflmmtory response is mde more efficient. The impct of trce minerls from Zinpro Performnce Minerls on production nimls is not limited to the current genertion, ut is lso communicted to the next genertion... Interntionl Inflmmtion Symposium 217 Performnce Minerls is registered trdemrk of Zinpro Corp. 217 Zinpro Corp. All rights reserved. Inflmmtion-11.17