Associations among serum pro- and anti-inflammatory cytokines, metabolic mediators, body condition, and uterine disease in postpartum dairy cows

Reproductive Biology and Endocrinology

John P Kastelic¹  Dale A Moore³  Erin J Jeffress²  Jesse R Olsen³  Vanmathy R Kasimanickam³  Ramanathan K Kasimanickam³ 

[1] Department of Production Animal Health, University of Calgary, Calgary AB T2N 4N1, Canada;Center for Veterinary and Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA;Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA 99164, USA

关键词: Dairy cows;    Body condition;    Uterine inflammation;    Postpartum;    IGF-1;    Insulin;    Adipokines;   

Others  :  809891
DOI  :  10.1186/1477-7827-11-103

 received in 2013-04-19, accepted in 2013-10-29,  发布年份 2013

【 摘 要 】

Background

Adipose tissue is an active endocrine organ which secretes a wide range of hormones and protein factors, collectively termed adipokines. Adipokines affect appetite and satiety, glucose and lipid metabolism, inflammation and immune functions. The objectives were to evaluate serum concentrations of adipokines (adiponectin, leptin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6) in lactating dairy cows with postpartum uterine inflammatory conditions (metritis, clinical endometritis or subclinical endometritis) and in cows experiencing loss of body condition, and to assess the relationship of adipokines and body condition loss in the establishment of persistent uterine inflammatory conditions.

Methods

Lactating multiparous Holstein cows (N = 40), with body condition scores (BCS) from 2 to 4 (eight cows for each 0.5 score increment) were enrolled. Body condition was monitored for all cows weekly for 7 weeks post calving; cows with uterine inflammatory conditions were also re-evaluated 2 weeks later. Blood samples were collected from 1 week prior to calving to 7 weeks after calving for determination of serum concentrations of adipokines, insulin and insulin like growth factor (IGF)-1.

Results

Cows with metritis or clinical endometritis had higher serum concentrations of adiponectin, leptin, TNF-alpha, IL-1beta and IL-6 compared to normal cows (P < 0.05). Furthermore, serum leptin, TNF-alpha, IL-1beta and IL-6 were higher in cows with subclinical endometritis compared to normal cows (P < 0.05), and insulin and IGF-1 concentrations were lower in cows with metritis or clinical endometritis. Cows with low BCS (2 and 2.5) had significantly higher adiponectin, TNF-alpha, IL-1beta and IL-6 than those with high BCS (3 to 4). Cows with persistent uterine inflammatory conditions had higher adiponectin, leptin TNF-alpha, IL-1beta and IL-6 and insulin compared to normal and spontaneously recovered cows, except for IGF-1 (P < 0.05).

Conclusions

Serum concentrations of adipokines, insulin, and IGF-1 had significant associations with BCS categories (low vs. high) and postpartum uterine inflammatory conditions. Perhaps loss of body condition mediated increases in anti- and pro-inflammatory cytokines, whereas increased pro- and anti-inflammatory cytokines concentrations mediated body condition loss and thereby prolonged persistence of uterine inflammation in dairy cows.

【 授权许可】

   
2013 Kasimanickam et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Fourichon C, Seegers H, Malher X: Effect of disease on reproduction in the dairy cow: a meta-analysis. Theriogenology 2000, 53:1729-1759.
• [2]Sheldon IM, Price SB, Cronin J, Gilbert RO, Gadsby JE: Mechanisms of infertility associated with clinical and subclinical endometritis in high producing dairy cattle. Reprod Domest Anim 2009, 44(Suppl 3):1-9.
• [3]Kasimanickam R, Duffield TF, Foster RA, Gartley CJ, Leslie KE, Walton JS, Johnson WH: Endometrial cytology and ultrasonography for the detection of subclinical endometritis in postpartum dairy cows. Theriogenology 2004, 62:9-23.
• [4]LeBlanc SJ, Duffield TF, Leslie KE, Bateman KG, Keefe GP, Walton JS, Johnson WH: Defining and diagnosing postpartum clinical endometritis and its impact on reproductive performance in dairy cows. J Dairy Sci 2002, 85:2223-2236.
• [5]Sheldon IM, Lewis GS, LeBlanc S, Gilbert RO: Defining postpartum uterine disease in cattle. Theriogenology 2006, 65:1516-1530.
• [6]Bondurant RH: Inflammation in the bovine female reproductive tract. J Dairy Sci 1999, 82:101-110.
• [7]Singh J, Murray RD, Mshelia G, Woldehiwet Z: The immune status of the bovine uterus during the peripartum period. Vet J 2008, 175:301-309.
• [8]Sheldon IM, Cronin J, Goetze L, Donofrio G, Schuberth HJ: Defining postpartum uterine disease and the mechanisms of infection and immunity in the female reproductive tract in cattle. Biol Reprod 2009, 81:1025-1032.
• [9]Cai TQ, Weston PG, Lund LA, Brodie B, McKenna DJ, Wagner WC: Association between neutrophil function and periparturient disorders in cows. Am J Vet Res 1994, 55:934-943.
• [10]Hammon DS, Evjen IM, Dhiman TR, Goff JP, Walters JL: Neutrophil function and energy status in Holstein cows with uterine health disorders. Vet Immunol Immunopathol 2006, 113:21-29.
• [11]Huzzey JM, Veira DM, Weary DM, von Keyserlingk MA: Prepartum behavior and dry matter intake identify dairy cows at risk for metritis. J Dairy Sci 2007, 90:3220-3233.
• [12]Urton G, von Keyserlingk MA, Weary DM: Feeding behavior identifies dairy cows at risk for metritis. J Dairy Sci 2005, 88:2843-2849.
• [13]Plata-Salaman CR: Cytokines and feeding suppression: an integrative view from neurologic to molecular levels. Nutrition 1995, 11:674-677.
• [14]Hotamisligil GS: Inflammation and metabolic disorders. Nature 2006, 444:860e7.
• [15]Tilg H, Moschen AR: Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immuno 2006, 6:772e83.
• [16]Guerre-Millo M: Adiponectin: an update. Diabetes Metab 2008, 34:12-18.
• [17]Whitehead JP, Richards AA, Hickman IJ, Macdonald GA, Prins JB: Adiponectin - a key adipokine in the metabolic syndrome. Diabetes Obes Metab 2006, 8:264-280.
• [18]Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B: Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006, 17:4-12.
• [19]Ingvartsen KL, Biosclair YR: Leptin and the regulation of food intake, energy homeostasis and immunity with special focus on periparturient ruminants. Dom Anim Endocrinol 2001, 21:215-250.
• [20]Liefers SC, Veerkamp RF, te Pas MFW, Delavaud C, Chilliard Y, van der Lende T: Leptin concentrations in relation to energy balance, milk yield, intake, live weight, and estrus in dairy cows. J Dairy Sci 2003, 86:799-807.
• [21]Schoenberg KM, Perfield KL JK, Bradford BJ, Boisclair YR, Overton TR: Effects of prepartum 2,4-thiazolidinedione on insulin sensitivity, plasma concentrations of tumor necrosis factor-α and leptin, and adipose tissue gene expression. J Dairy Sci 2011, 94:5523-5532.
• [22]Havel PJ: Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Opin Lipidol 2002, 13:51-59.
• [23]Havel PJ: Role of adipose tissue in body-weight regulation: mechanisms regulating leptin production and energy balance. Proc Nutr Soc 2000, 59:359-371.
• [24]Ferguson JD, Galligan DT, Thomsen N: Principal descriptors of body condition score in Holstein cows. J Dairy Sci 1994, 77:2695-2703.
• [25]Benzaquen ME, Risco CA, Archbald LF, Melendez P, Thatcher MJ, Thatcher WW: Rectal temperature, calving-related factors, and the incidence of puerperal metritis in postpartum dairy cows. J Dairy Sci 2007, 90:2804-2814.
• [26]Sinha MK, Songer T, Xiao Q, Sloan JH, Wang J, Ji S, Alborn WE, Davis RA, Swarbrick MM, Stanhope KL, Wolfe BM, Havel PJ, Schraw T, Konrad RJ, Scherer PE, Mistry JS: Analytical validation and biological evaluation of a high molecular-weight adiponectin ELISA. Clin Chem 2007, 53:2144-2151.
• [27]Tvarijonaviciute A, Martínez-Subiela S, Ceron JJ: Validation of 2 commercially available enzyme-linked immunosorbent assays for adiponectin determination in canine serum samples. Can J Vet Res 2010, 74:279-285.
• [28]Reed GF, Lynn F, Meade BD: Use of coefficient of variation in assessing variability of quantitative assays. Clin Diagn Lab Immunol 2002, 9:1235-1239.
• [29]Herath S, Lilly ST, Santos NR, Gilbert RO, Goetze L, Bryant CE, White JO, Cronin J, Sheldon IM: Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility. Reprod Biol Endocrinol 2009, 7:55. BioMed Central Full Text
• [30]Moschen AR, Molnar C, Geiger S, Graziadei I, Ebenbichler CF, Weiss H, Kaser S, Kaser A, Tilg H: Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor alpha expression. Gut 2010, 59:1259-1264.
• [31]Morley JE, Thomas DR, Wilson M-MG: Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr 2006, 83:735-743.
• [32]Ishikawa Y, Nakada K, Hagiwara K, Kirisawa R, Iwai H, Moriyoshi M, Sawamukai Y: Changes in interleukin-6 concentration in peripheral blood of pre- and postpartum dairy cattle and its relationship to postpartum reproductive performance disease. J Vet Med Sci 2004, 66:1403-1418.
• [33]Gabler C, Fischer C, Drillich M, Einspanier R, Heuwieser W: Time-dependent mRNA expression of selected pro-inflammatory factors in the endometrium of primiparous cows postpartum. Reprod Biol Endocrinol 2010, 8:152. BioMed Central Full Text
• [34]Fischer C, Drillich M, Odau S, Heuwieser W, Einspanier R, Gabler C: Selected pro-inflammatory factor transcripts in bovine endometrial epithelial cells are regulated during the oestrous cycle and elevated in case of subclinical or clinical endometritis. Reprod Fertil Dev 2010, 22:818-829.
• [35]Galvão KN, Santos NR, Galvão JS, Gilbert RO: Association between endometritis and endometrial cytokine expression in postpartum Holstein cows. Theriogenology 2011, 76:290-299.
• [36]van Hall G, Steensberg A, Sacchetti M, Fischer C, Keller C, Schjerling P, Hiscock N, Møller K, Saltin B, Febbraio MA, Pedersen BK: Interleukin-6 stimulates lipolysis and fat oxidation in humans. J Clin Endocrinol Metab 2003, 88:3005-3010.
• [37]Jacobi SK, Gabler NK, Ajuwon KM, Davis JE, Spurlock ME: Adopicytes, myofibers and cytokine biology: new horizons in the regulation of growth and body composition. J Anim Sci 2006, 85:E140-E149.
• [38]Klasing KC, Laurin DE, Peng RK, Fry DM: Immunologically mediated growth depression in chicks: Influence of feed intake, corticosterone and interleukin-1. J Nutr 1987, 117:1629-1637.
• [39]Richards C, Gauldie J, Baumann H: Cytokine control of acute phase protein expression. Eur Cytokine Netw 1991, 2:89-98.
• [40]Dinarello CA: Blocking IL-1 in systemic inflammation. J Exp Med 2005, 201:1355-1359.
• [41]Tache´ Y, Saperas E: Central actions on interleukin 1 on gastrointestinal function. In Neurobiology of Cytokines, Part B. Edited by De Souza EB. New York: Academic Press; 1993:169-184.
• [42]Plata-Salaman CR, Borkoski JP: Chemokines/intercrines and central regulation of feeding. Am J Physiol 1994, 266:R1711-R1715.
• [43]Hunt JS, Chen HL, Hu XL, Tabibzadeh S: Tumor necrosis factor-alpha messenger ribonucleic acid and protein in human endometrium. Biol Reprod 1992, 47:141-147.
• [44]Worku M, Morris A: Binding of different forms of lipopolysaccharide and gene expression in bovine blood neutrophils. J Dairy Sci 2009, 92:3185-3193.
• [45]Okuda K, Sakumoto R, Okamoto N, Acosta TJ, Abe H, Okada H, Sinowatz F, Skarzynski DJ: Cellular localization of genes and proteins for tumor necrosis factor-α (TNF), TNF receptor types I and II in bovine endometrium. Mol Cell Endocrinol 2010, 330:41-48.
• [46]Okuda K, Kasahara Y, Murakami S, Takahashi H, Woclawek-Potocka I, Skarzynski DJ: Interferon-tau blocks the stimulatory effect of tumor necrosis factor-alpha on prostaglandin F2alpha synthesis by bovine endometrial stromal cells. Biol Reprod 2004, 70:191-197.
• [47]Lindell JO, Kindahl H, Jansson L, Edqvist LE: Post-partum release of prostaglandin F2a and uterine involution in the cow. Theriogenology 1982, 17:237-245.
• [48]Del Vecchio RP, Matsas DJ, Inzana TJ, Sponenberg DP, Lewis GS: Effect of intrauterine bacterial infusions and subsequent endometritis on prostaglandin F2 alpha metabolite concentrations in postpartum beef cows. J Anim Sci 1992, 70:3158-3162.
• [49]Mateus L, Lopes da Costa L, Diniz P, Ziecik AJ: Relationship between endotoxin and prostaglandin (PGE2 and PGFM) concentrations and ovarian function in dairy cows with puerperal endometritis. Anim Reprod Sci 2003, 76:143-154.
• [50]Rasmussen MS, Lihn AS, Pedersen SB, Bruun JM, Rasmussen M, Richelsen B: Adiponectin receptors in human adipose tissue: effects of obesity, weight loss, and fat depots. Obesity (Silver Spring) 2006, 14:28-35.
• [51]Kim MJ, Maachi M, Debard C, Loizon E, Clément K, Bruckert E, Hainque B, Capeau J, Vidal H, Bastard JP: Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose tolerant obese subjects during weight loss. Eur J Endocrinol 2006, 155:161-165.
• [52]Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T: The fat-derived hormone adiponectin reverses insulin resistance associated with both lipo-atrophy and obesity. Nat Med 2001, 7:941-946.
• [53]Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, Paschke R: Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2003, 301:1045-1050.
• [54]Gregory NG: Physiological mechanisms causing sickness behaviour and suffering in diseased animals. Anim Welf 1998, 7:293-305.
• [55]van Deuren M, Dofferhoff ASM, van der Meer JWM: Cytokines and the response to infection. J Pathol 1992, 168:349-356.
• [56]Perlstein RS, Whitnall MH, Abrams JS, Mougey EH, Neta R: Synergistic roles of interleukin-6, interleukin-1, and tumor necrosis factor in the adrenocorticotropin response to bacterial lipopolysaccharide in vivo. Endocrinology 1993, 132:946-952.
• [57]van der Meer MJM, Sweep CGJ, Pesman GJ, Borm GF, Hermus ARMM: Synergism between IL-1b and TNF-a on the activity of the pituitary-adrenal axis and on food intake of rats. Am J Physiol 1995, 268:E551-E557.
• [58]Yang ZJ, Koskeki M, Meguid M, Gleason JR, Debonis D: Synergistic effect of rhTNF-a and rhIL-1a in inducing anorexia in rats. Am J Physiol 1994, 267:R1056-R1064.
• [59]Kerestes M, Faigl V, Kulcsár M, Balogh O, Földi J, Fébel H, Chilliard Y, Huszenicza G: Periparturient insulin secretion and whole-body insulin responsiveness in dairy cows showing various forms of ketone pattern with or without puerperal metritis. Domest Anim Endocrinol 2009, 37:250-261.
• [60]Cronin JG, Turner ML, Goetze L, Bryant CE, Sheldon IM: Toll-like receptor 4 and MYD88-dependent signaling mechanisms of the innate immune system are essential for the response to lipopolysaccharide by epithelial and stromal cells of the bovine endometrium. Biol Reprod 2012, 86:51.
• [61]Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW: Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 1997, 82:4196-4200.
• [62]Buyalos RP, Funari VA, Azziz R, Watson JM, Martinez-Maza O: Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology. Fertil Steril 1992, 58:302-306.
• [63]Wang HS, Kanzaki H, Yoshida M, Sato S, Tokushige M, Mori T: Suppression of lymphocyte reactivity in vitro by supernatants of explants of human endometriosis. Am J Obstet Gynecol 1987, 157:956-963.
• [64]Steele RW, Dmowski WP, Marmer DJ: Immunologic aspects of human endometriosis. Am J Reprod Immunol 1984, 6:3-36.
• [65]McCarthy SD, Waters SM, Kenny DA, Diskin MG, Fitzpatrick R, Patton J, Wathes DC, Morris DG: Negative energy balance and hepatic gene expression patterns in high-yielding dairy cows during the early postpartum period: a global approach. Physiol Genomics 2010, 42A:188-199.