In conclusion, patients with allergic rhinitis have a marked increase in serum levels of leptin but a decrease in adiponectin levels. These data confirm a
relevant role for adipokines in the pathogenesis of allergic rhinitis and suggest important therapeutic implications that need further exploration.
31
Table I: Anthropometric parameters and serum leptin, adiponectin, eosinophil cationic protein (ECP), total IgE and mite-specific IgE levels in children with allergic rhinitis and healthy controls*
Total 125.08±14.20 119.57±16.83 .082
Girls 124.06±15.61 119.40±18.37 .437
Total 30.36 (21.08-41.85) 39.07 (30.83-45.46) .005
Girls 34.69 (23.11-44.19) 41.62 (34.18-49.27) .180
Boys 26.97 (20.97-36.83) 37.27 (28.46-43.34) .009
ECP (ng/L) 21.40 (7.40-40.1) 6.86 (4.16-16.1) .018
Total Ig E (IU/ml) 356 (169.5-672.5) 32.6 (18.85-83.85) .000
IgE to D.p†
. (IU/ml) 61.4 (12.15-100) < 0.35 .000
IgE to D.f.†
(IU/ml) 48.0 (9.57-100) < 0.35 .000
*Age, weight, height and BMI are given as arithmetic means ± SDs; The Student t test is used.
Leptin, adiponectin, ECP, IgE , IgE to D.p. and IgE to D.f. are given as median (interquartile range); the Mann-Whitney U test is used for comparison.
†D.p.: Dermatophagoides pteronyssinus
†D.f.: Dermatophagoides farinae
Table II Association of leptin and adiponectin levels with anthropometric and allergic inflammatory parameters in in children with allhinitiergic rs and healthy controls
Correlation coefficient
Leptin Adiponectin Parameter
Partients Controls Partients Controls BMI 0.67a 0.45b -0.36b -0.54a
The correlation coefficient was calculated with Pearson’s correlation analysis. Data are given for both genders combined. NS, Not significant; NA, not assessed.
aP < 0.001
bP < 0.01
cP < 0.05
Table III. Multivariate regression analysis for leptin concentration* Regression
coefficients (β) SE t Statistic P value
Constant -2.162 0.749 -2.89 0.0049 BMI 0.140 0.023 6.21 < 0.0001
Sex 0.109 0.055 1.97 0.052
Age 0.031 0.022 1.41 0.163
Allergic
rhinitis 0.100 0.052 2.01 0.040 Adiponetin 0.140 0.348 0.40 0.687
*The dependent variable was log leptin (adjusted R2= 0.35; F = 11.45; p < 0.0001)
33
Table IV. Multivariate regression analysis for adiponectin concentration*
Regression
coefficients (β) SE t Statistic P value
Constant 1.916 0.122 15.65 < 0.0001 BMI -0.018 0.008 -2.36 0.020
Sex 0.011 0.017 0.67 0.504
Age -0.014 0.007 -2.19 0.031 Allergic
rhinitis -0.040 0.015 -2.58 0.011 Leptin 0.013 0.031 0.40 0.688 The dependent variable was log adiponectin (adjusted R2=0.20; F=5.611; p = 0.0001)
Table V. Multivariate logistic regression analysis for the determination of risk factors for the development of allergic rhinitis
P value Odds ratio 95% confidence interval Log leptin 0.045 27.06 1.01-1209 Log adiponectin 0.013 13.14 1.84-115.1
BMI 0.365 4.07 0.21-98.76
Age 0.553 0.56 0.08-3.78
Sex 0.719 0.84 0.31-2.22
參考文獻
1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM.
Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-32.
2. Maffei M, Fei H, Lee GH, Dani C, Leroy P, Zhang Y, et al. Increased
expression in adipocytes of ob RNA in mice with lesions of the hypothalamus and with mutations at the db locus. Proc Natl Acad Sci U S A
1995;92:6957-60.
3. Elmquist JK. Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin. Physiol Behav 2001;74:703-8.
4. Huang L, Li C. Leptin: a multifunctional hormone. Cell Res 2000;10:81-92.
5. Gainsford T, Willson TA, Metcalf D, Handman E, McFarlane C, Ng A, et al.
Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci U S A 1996;93:14564-8.
6. Umemoto Y, Tsuji K, Yang FC, Ebihara Y, Kaneko A, Furukawa S, et al.
Leptin stimulates the proliferation of murine myelocytic and primitive hematopoietic progenitor cells. Blood 1997;90:3438-43.
7. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation induced
immunosuppression. Nature 1998;394:897-901.
8. Sanchez-Margalet V, Martin-Romero C, Santos-Alvarez J, Goberna R, Najib S, Gonzalez-Yanes C. Role of leptin as an immunomodulator of blood
35
mononuclear cells: mechanisms of action. Clin Exp Immunol 2003;133:11-9.
9. Martin-Romero C, Santos-Alvarez J, Goberna R, Sanchez-Margalet V.
Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell Immunol 2000;199:15-24.
10. Bouloumie A, Marumo T, Lafontan M, Busse R. Leptin induces oxidative stress in human endothelial cells. FASEB J 1999;13:1231-8.
11. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996;271:10697-703.
12. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941-6.
13. Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G. Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes 2003;52:1779-85.
14. Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, et al.
Association between adiponectin and mediators of inflammation in obese women. Diabetes 2003;52:942-7.
15. Masaki T, Chiba S, Tatsukawa H, Yasuda T, Noguchi H, Seike M, et al.
Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice. Hepatology 2004;40:177-84.
16. Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, et al.
Adiponectin specifically increased tissue inhibitor of metalloprotenase-1
through interleukin-10 expression in human macrophages.Circulation 2004;109:2046-9.
17. Wolf AM, Wolf D, Rumpold H, Enrich B, Tilg H. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes.
Biochem Biophys Res Commun 2004;323:630-5.
18. Wulster-Radcliffe MC, Ajuwon KM, Wang J, Christian JA, Spurlock ME.
Adiponectin differentially regulate cytokines in porcine macrophages.
Biochem Biophys Res Commun 2004;316:924-9.
19. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, et al. novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999;100:2473-6.
20. Kawanami D, Maemura K, Takeda N, Harada T, Nojiri T, Imai Y, et al.
Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun 2004;314:415-9.
21. Chinn S. Obesity and asthma: evidence for and against a causal relation. J Asthma 2003;40:1–16.
22. Chinn S, Jarvis D, Burney P. Relation of bronchial responsiveness to body mass index in the ECRHS. European Community Respiratory Health Survey.
Thorax 2002;57:1028–33.
23. Figueroa-Munoz JI, Chinn S, Rona RJ. Association between obesity and asthma in 4–11 year old children in the UK. Thorax 2001;56:133–7.
37
24. Camargo CA Jr, Weiss ST, Zhang S, et al. Prospective study of body mass index, weight change, and risk of adult- onset asthma in women. Arch Intern Med 1999;159:2582–8
25. Shore SA, Schwartzman IN, Mellema MS, Flynt L, Imrich A, Johnston RA.
Effect of leptin on allergic airway responses in mice. J Allergy Clin Immunol 2005;115:103–109.
26. Shore SA, Terry RD, Flynt L, Xu A, Hug C. Adiponectin attenuates
allergen-induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol 2006;118:389-95.
27. Guler N, Kirerleri E, Ones U, Tamay Z, Salmayenli N, Darendeliler F.
Leptin: does it have any role in childhood asthma? J Allergy Clin Immunol 2004;114:254–259.
28. Sood A, Ford ES, Camargo CA. Association between leptin and asthma in adults. Thorax 2006;61:300–305.
29. Nathan RA, Meltzer EO, Selner JC, Storms W. Prevalence of allergic rhinitis in the United States. J Allergy Clin Immunol 1997;99(suppl):S808-14.
30. Wright AL, Holberg CJ, Martinez FD, Halonen M, Morgan W, Taussig LM.
Epidemiology of physician-diagnosed allergic rhinitis in childhood.Pediatrics 1994;94:895-901.
31. Passalacqua G, Ciprandi G, Canonica GW. The nose–lung interaction in allergic rhinitis and asthma: united airways disease. Curr Opin Allergy Clin Immunol 2001;1:7–13.
32. Clough J. The effect of gender on the prevalence of atopy and asthma. Clin Exp Allergy 1993;23:883-5.
33. Bousquet J, van Cauwenberge P, Khaltaev N. ARIA workshop report allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001;108:147s–334s
34. Blum WF, Englaro P, Hanitsch S, Juul A, Hertel NT, Müller J, et al. Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage and testosterone. J Clin
Endocrinol Metab 1997;82:2904-10.
35. Garcia-Mayor RV, Andrade MA, Rios M, Lage M, Dieguez C, Casanueva FF. Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage. J Clin
Endocrinol Metab 1997;82:2849-55.
36. Hassink SG, Sheslow DV, Lancey E, Opentanova I, Considine RV, Caro JF.
Serum leptin in children with obesity: relationship to gender and development. Pediatrics 1996;98:201-3.
37. Punthakee Z, Delvin EE, O’Loughlin J, Paradis G, Levy E, Platt RW, Lambert M Adiponectin, Adiposity, and Insulin Resistance in Children and Adolescents. J. Clin. Endocrinol. Metab., Jun 2006; 91: 2119 – 2125
38. Böttner A, Kratzsch J, Müller G, Kapellen TM, Blüher S, Keller E, Blüher M, Kiess W. Gender Differences of Adiponectin Levels Develop during the Progression of Puberty and Are Related to Serum Androgen Levels. J. Clin.
39
Endocrinol. Metab 2004; 89: 4053 - 4061
38. Tuzun A, Uygun A, Yesilova Z, Ozel AM, Erdil A, Yaman H, et al. Leptin levels in the acute stage of ulcerative colitis. J Gastroenterol Hepatol
2004;19:429-32.
39. Barbier M, Vidal H, Desreumaux P, Dubuquoy L, Bourreille A, Colombel JF, et al. Overexpression of leptin mRNA in mesenteric adipose tissue in inflammatory bowel diseases. Gastroenterol Clin Biol 2003;27:987-91.
40. Otero M, Lago R, Gomez R, Lago F, Dieguez C, Gómez-Reino JJ, Gualillo O. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis. Ann Rheum Dis 2006;65:1198–1201.
41. Batocchi AP, Rotondi M, Caggiula M, Frisullo G, Odoardi F, Nociti V, et al.
Leptin as a marker of multiple sclerosis activity in patients treated with interferon-beta. J Neuroimmunol 2003;139:150-4.
42. Takeshita S, Takabayashi H, Yoshida N. Circulating adiponectin levels in Kawasaki disease. Acta Paediatr. 2006;95:1312-4.
43. Takemura Y, Osuga Y, Harada M, Hirata T, Koga K, Morimoto C, Hirota Y, Yoshino O, Yano T, Taketani Y. Serum adiponectin concentrations are decreased in women with endometriosis.Hum Reprod. 2005;20:3510-3 44. Gurkan F, Atamer Y, Ece A, Kocyigit Y, Tuzun H, Mete N. Serum leptin
levels in asthmatic children treated with an inhaled corticosteroid. Ann Allergy Asthma Immunol 2004;93:277–280.
45. Kimata H. Elevated serum leptin in AEDS [letter]. Allergy.2002;57:179.
46. Grunfeld C, Zhao C, Fuller J, Pollack A, Moser A, Friedman J, et al.
Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. J Clin Invest 1996;97:2152-7.
47. Degawa-Yamauchi M, Moss KA, Bovenkerk JE, Shankar SS, Morrison CL, Lelliott CJ, et al. Regulation of adiponectin expression in human adipocytes:
effects of adiposity, glucocorticoids, and tumor necrosis factor alpha. Obes Res 2005;13:662-9.
48. Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, Astrup A &
RichelsenB 2003 Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. American Journal of Physiology.Endocrinology and Metabolism 285 E527–E533.
49. Kanehiro A, Lahn M, Makela MJ, Dakhama A, Joetham A, Rha YH, et al.
Requirement for the p75 TNF-alpha receptor 2 in the regulation of airway hyperresponsiveness by gamma delta T cells. J Immunol 2002;169:4190-7.
50. Iwasaki M, Saito K, Takemura M, Sekikawa K, Fujii H, Yamada Y, Wada H, Mizuta K, Seishima M, Ito Y. TNF-α contributes to the development of
allergic rhinitis in mice J Allergy Clin Immunol 2003;112:134-40.
51. Nakae S, Komiyama Y, Yokoyama H, Nambu A, Umeda M, Iwase M, et al.
IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response. Int Immunol 2003;15:483-90.
41
52. Amici MD, Puggioni F, Casali L, Alesina R. Variations in serum levels of interleukin (IL)-1b, IL-2, IL-6, and tumor necrosis factor-a during specific immunotherapy. Ann Allergy Asthma Immunol 2001;86:311–313.
53. Hetland G, Granum B, Groeng EC, Lovik M. Leptin does not influence the IgE response to ovalbumin in mice. Clin Immunol.2001;101:8–11.
54 Conus S, Bruno A, Simon HU. Leptin is an eosinophil survival factor. J Allergy Clin Immunol 2005;116:1228-34
55. Hsu PY, Yang YH, Lin YT, Chiang BL. Serum eosinophil cationic protein level and disease activity in childhood rhinitis. Asian Pac J Allergy Immunol 2004;22:19-24.
56. Togias A. Systemic effects of local allergic disease. J Allergy Clin Immunol 2004;113:S8-14.
57. Borish L. Allergic rhinitis: Systemic inflammation and implications for management. J Allergy Clin Immunol 2003;112:1021-31.