The discovery of how gender influences age immunological mechanisms in health and disease, and the identification of ageing gender-specific biomarkers, could lead to specifically tailored treatment and ultimately improve therapeutic success rates

Immunity and Ageing

Volumn 9, Issue , 2012, Pages

  Berghella, Anna M ^a,b   Contasta, Ida ^a   Del Beato, Tiziana ^a   Pellegrini, Patrizia ^a  

^a INSTITUTE OF TRANSLATIONAL PHARMACOLOGY   (Italy)

^b Istituto di Farmacologia Traslazionale   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 12; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; GLUCOCORTICOID RECEPTOR; HLA DQ8 ANTIGEN; HLA DRB1 ANTIGEN; INTERLEUKIN 2; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE; MYELOID DIFFERENTIATION FACTOR 88; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; NITROGEN OXIDE; PROGRAMMED DEATH 1 LIGAND 1; RAC1 PROTEIN; REACTIVE OXYGEN METABOLITE; RETINOID X RECEPTOR ALPHA; STAT5 PROTEIN; SULFUR; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 7;

AGING; ARTHRITIS; ARTICLE; AUTISM; B LYMPHOCYTE ACTIVATION; CD8+ T LYMPHOCYTE; CHRONIC PAIN; CYTOKINE RELEASE; DISEASE ASSOCIATION; GROWTH DISORDER; HEPATITIS C; HUMAN; IMMUNE RESPONSE; INFECTION; INSULIN DEPENDENT DIABETES MELLITUS; KAPOSI SARCOMA; LIVER CELL CARCINOMA; LUPUS ERYTHEMATOSUS NEPHRITIS; MELANOMA; PERSONALIZED MEDICINE; PRIORITY JOURNAL; SEX DIFFERENCE; SYSTEMIC LUPUS ERYTHEMATOSUS; T LYMPHOCYTE ACTIVATION; TH1 CELL; TH2 CELL;

EID: 84872550311     PISSN: None     EISSN: 17424933     Source Type: Journal    
DOI: 10.1186/1742-4933-9-24     Document Type: Article

References (65)

1. Licastro F, Caruso C. Predictive diagnostics and personalized medicine for the prevention of chronic degenerative diseases. Immun Ageing 2010, 16:7.
2. Martin KJ, Fournier MV, Reddy GP, Pardee AB. A need for basic research on fluid-based early detection biomarkers. Cancer Research 2010, 70:5203-6. 10.1158/0008-5472.CAN-10-0987, 20587531.
3. Liu LY, Schaub MA, Sirota M, Butte AJ. Sex differences in disease risk from reported genome-wide association study findings. Hum Genet 2012, 131:353-64. 10.1007/s00439-011-1081-y, 21858542.
4. Grossman CJ. Possible underlying mechanisms of sexual dimorphism in the immune response, fact and hypothesis. Journal of Steroid Biochemistry 1989, 34:241-251. 10.1016/0022-4731(89)90088-5, 2696846.
5. Schuurs AH, Verhuel HA. Effects of gender and sex steroids on the immune response. Journal of Steroid Biochemistry 1990, 35:157-172. 10.1016/0022-4731(90)90270-3, 2407902.
6. Cannon JC, St-Pierre BA. Gender differences in host defense mechanisms. Journal of Psychiatric Research 1997, 31:99-113. 10.1016/S0022-3956(96)00055-6, 9201652.
7. Rhodes K, Scott A, Markhan RL, Monk-Jones ME. Immunological sex differences. Annals of Rheumatic Diseases 1969, 28:104-120.
8. Butterworth MB, McClellan B, Alansmith M. Influence of sex on immunoglobulin levels. Nature 1967, 214:1224-1225. 10.1038/2141224a0, 4169229.
9. Terres G, Morrison SL, Habicht GH. Quantitative difference in the immune response between male and female mice. Proceedings of the Society for Experimental Biology and Medicine 1968, 127:664-667.
10. Morell V. Zeroing in on how hormones affect the immune system. Science 1995, 269:773-775. 10.1126/science.7638587, 7638587.
11. Homo-Delarche F, Fitzpatrick F, Christeff N, Nunez E, Bach JF, Dardenne M. Sex steroids, glucocorticoids, stress and autoimmunity. The Journal of Steroid Biochemistry and Molecular Biology 1991, 40:619-637. 10.1016/0960-0760(91)90285-D, 1958562.
12. Grossman CJ. Regulation of the immune system by sex steroids. Endocrine Reviews 1984, 5:435-455. 10.1210/edrv-5-3-435, 6381037.
13. Pietschmann P, Gollob E, Brosch S, Hahn P, Kudlacek S, Willheim M, Woloszczuk W, Peterlik M, Tragl KH. The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism. Exp Gerontol 2003, 38:1119-27. 10.1016/S0531-5565(03)00189-X, 14580865.
14. Khosla S, Melton LJ, Atkinson EJ, O'Fallon WM, Klee GG, Riggs BL. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role of bioavailable estrogen. J Clin Endocrinol Metab 1998, 83:2266-2274. 10.1210/jc.83.7.2266, 9661593.
15. Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg I. Estradiol in elderly men. Aging Male 2002, 5:98-102.
16. Dolomie-Fagour L, Gatta B, Nguyen TDT, Corcuff JB. Bioavailable estradiol in man: Relationship with age and testosterone. Clin Chim Acta 2008, 398:145-147. 10.1016/j.cca.2008.09.005, 18824161.
17. Zhu BT, Han GZ, Shim JY, Wen Y, Jiang XR. Quantitative structure- activity relationship of various endogenous estrogen metabolites for human estrogen receptor α and β subtypes: Insights into the structural determinants favoring a differential subtype binding. Endocrinol 2006, 147:4132-4150.
18. Li J, McMurray RW. Effects of estrogen subtype-selective agonists on immune functions in ovariectomized mice. Int Immunopharmacol 2006, 6:1413-1423. 10.1016/j.intimp.2006.04.019, 16846835.
19. Terres G, Morrison SL, Habicht GS. A quantitative difference in the immune response between male and female mice. Proc Soc Exp Biol Med 1968, 127:664-667.
20. Beery TA. Sex differences in infection and sepsis. Crit Care Nurs Clin North Am 2003, 15:55-62. 10.1016/S0899-5885(02)00028-X, 12597040.
21. Gellin BG, Broome CV. Listeriosis. JAMA 1989, 261:1313-1320. 10.1001/jama.1989.03420090077035, 2492614.
22. Pasche B, Kalaydjiev S, Franz TJ, Kremmer E, Gailus-Durner V, Fuchs H. Hrabé de Angelis M, Lengeling A, Busch DH: Sex-dependent susceptibility to Listeria monocytogenes infection is mediated by differential interleukin-10 production. Infect Immun 2005, 73:5952-5960. 10.1128/IAI.73.9.5952-5960.2005, 1231091, 16113316.
23. Petrilli V, Dostert C, Muruve DA, Tschopp J. The inflammasome:Adanger sensing complex triggering innate immunity. Curr Opin Immunol 2007, 19:615-622. 10.1016/j.coi.2007.09.002, 17977705.
24. Martinon F, Burns K, Tschopp J. The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 2002, 10:417-426. 10.1016/S1097-2765(02)00599-3, 12191486.
25. Wang S, Miura M, Jung YK, Zhu H, Li E, Yuan J. Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE. Cell 1998, 92:501-509. 10.1016/S0092-8674(00)80943-5, 9491891.
26. Saleh M, Mathison JC, Wolinski MK, Bensinger SJ, Fitzgerald P, Droin N, Ulevitch RJ, Green DR, Nicholson DW. Enhanced bacterial clearance and sepsis resistance in caspase-12 deficient mice. Nature 2006, 440:1064-1068. 10.1038/nature04656, 16625199.
27. Yeretssian G, Doiron K, Shao W, Leavitt BR, Hayden MR, Nicholson DW, Saleh M. Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes infection. Proc Natl Acad Sci U S A 2009, 106:9016-20. 10.1073/pnas.0813362106, 2690057, 19447924.
28. Mosmann TR, Schumacher JH, Street NF, Budd R, O'Gara A, Fong TAT, Bond MW, Moore KWM, Sher A, Fiorentino DF. Diversity of cytokine synthesis and function of mouse CD4+ T cells. Immunol Rev 1991, 123:209-29. 10.1111/j.1600-065X.1991.tb00612.x, 1684780.
29. Coffman RL, Varkila K, Scott P, Chatelain R. Role of cytokines in the differentiation of CD4+ T-cell subsets in vivo. Immunol Rev 1991, 123:189-207. 10.1111/j.1600-065X.1991.tb00611.x, 1684779.
30. Peltz G. A role for CD4+ T cell subsets producing a selective pattern of lymphokines in the pathogenesis of human chronic inflammatory and allergic diseases. Immunol Rev 1991, 123:23-35. 10.1111/j.1600-065X.1991.tb00604.x, 1684781.
31. Murray JS, Madri J, Pasqualini T, Bottomly K. Functional CD4 T cell subset interplay in an intact immune system. J Immunol 1993, 150:4270-6.
32. Tai P, Wang J, Jin H, Song X, Yan J, Kang Y, Zhao L, An X, Du X, Chen X, Wang S, Xia G, Wang B. Induction of regulatory T cells by physiological level estrogen. J Cell Physiol 2008, 214:456-64. 10.1002/jcp.21221, 17654501.
33. Rook GA, Hernandez-Pando R, Lightman SL. Hormones, peripherally activated prohormones and regulation of the Th1/Th2 balance. Immunol Today 1994, 15:301-3. 10.1016/0167-5699(94)90075-2, 8086097.
34. Whitacre CC. Sex differences in autoimmune disease. Nat Immunol 2001, 9:777-80.
35. McCarthy M. The " gender gap" in autoimmune disease. Lancet 2000, 356:1088. 10.1016/S0140-6736(05)74535-9, 11009154.
36. Beageley KW, Gockel CM. Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol 2003, 38:13-22. 10.1016/S0928-8244(03)00202-5, 12900050.
37. Gleicher N. Some thoughts on the reproductive autoimmune failure syndrome (RAFS) and TH-1 versus TH-2 immune responses. Am J Reprod Immunol 2002, 48:252-4. 10.1034/j.1600-0897.2002.01111.x, 12516636.
38. Yakoo T, Takakuwa K, Ooki I, Kikuchi A, Tamura M, Tanaka K. Alterations of TH1 and TH2 cells by intracellular cytokine detection in patients with unexplained recurrent abortion before and after immunotherapy with the husband's mononuclear cells. Fertil Steril 2006, 85:1452-8. 10.1016/j.fertnstert.2005.10.058, 16647376.
39. Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafè M, Cavallone L, Franceschi C, Caruso C. Gender-specific association between -1082 IL-10 promoter polymorphism and longevity. Genes Immun 2002, 3:30-3. 10.1038/sj.gene.6363827, 11857058.
40. Franceschi C, Motta L, Valensin S, Rapisarda R, Franzone A, Berardelli M, Motta M, Monti D, Bonafè M, Ferrucci L, Deiana L, Pes GM, Carru C, Desole MS, Barbi C, Sartoni G, Gemelli C, Lescai F, Olivieri F, Marchegiani F, Cardelli M, Cavallone L, Gueresi P, Cossarizza A, Troiano L, Pini G, Sansoni P, Passeri G, Lisa R, Spazzafumo L, Amadio L, Giunta S, Stecconi R, Morresi R, Viticchi C, Mattace R, De Benedictis G, Baggio G. Do men and women follow different trajectories to reach extreme longevity? Italian Multicenter Study on Centenarians. Aging 2000, 12:77-84.
41. Balistreri CR, Candore G, Accardi G, Bova M, Buffa S, Bulati M, Forte GI, Listi F, Martorana A, Palmeri M, Pellicano M, Vaccarino L, Scola L, Lio D, Colonna-Romano G. Genetics of longevity. Data from the studies on Sicilian centenarians. Immun Ageing 2012, 9:8.
42. Palmeri M, Misiano G, Malaguarnera M, Forte GI, Vaccarino L, Milano S, Scola L, Caruso C, Motta M, Maugeri D, Lio D. Cytokine serum profile in a group of Sicilian nonagenarians. J Immunoassay Immunochem 2012, 33:82-90. 10.1080/15321819.2011.601781, 22181823.
43. Pellegrini P, Contasta I, Del Beato T, Ciccone F, Berghella AM. Gender-specific cytokine pathways, targets, and biomarkers for the switch from health to adenoma and colorectal cancer. Clin Dev Immunol 2011,
44. Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J 2001, 15:43-58. 10.1096/fj.99-1003rev, 11149892.
45. Thomson A. The Cytokine Handbook 1994, Academic, San Diego, Calif, USA.
46. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006, 441:235-238. 10.1038/nature04753, 16648838.
47. Korn T, Mitsdoerffer M, Croxford AL, Awasthi A, Dardalhon VA, Galileos G, Vollmar P, Stritesky GL, Kaplan MH, Waisman A, Kuchroo VK, Oukka M. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells. Proc Natl Acad Sci U S A 2008, 105:18460-5. 10.1073/pnas.0809850105, 2587589, 19015529.
48. Nowak EC, Weaver CT, Turner H, Begum-Haque S, Becher B, Schreiner B, Coyle AJ, Kasper LH, Noelle RJ. IL-9 as a mediator of Th17-driven inflammatory disease. J Exp Med 2009, 206:1653-1660. 10.1084/jem.20090246, 2722185, 19596803.
49. Oukka M. Th17 cells in immunity and autoimmunity. Annals of the Rheumatic Disease 2008, 67:26-9.
50. Cua DJ, Kastelein RA. TGFß a 'double agent' in the immune pathology war. Nature Immunology 2006, 7:557-9.
51. Korn T, Anderson AC, Bettelli E, Oukka M. The dynamics of effector T cells and Foxp3+ regulatory T cells in the promotion and regulation of autoimmune encephalomyelitis. Journal of Neuroimmunology 2007, 191:51-60. 10.1016/j.jneuroim.2007.09.009, 2289998, 17916388.
52. Greer JM, McCombe PA. Role of gender in multiple sclerosis: clinical effects and potential molecular mechanisms. J Neuroimmunol 2011, 234:7-18. 10.1016/j.jneuroim.2011.03.003, 21474189.
53. Zhou Y, Sonobe Y, Akahori T, Jin S, Kawanokuchi J, Noda M, Iwakura Y, Mizuno T, Suzumura A. IL-9 promotes Th17 cell migration into the central nervous system via CC chemokine ligand-20 produced by astrocytes. J Immunol 2011, 186:4415-21. 10.4049/jimmunol.1003307, 21346235.
54. Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, Sedgwick JD, Cua DJ. Divergent pro- and anti-inflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 2003, 198:1951-1957. 10.1084/jem.20030896, 2194162, 14662908.
55. Tzartos JS, Friese MA, Craner MJ, Palace J, Newcombe J, Esiri MM, Fugger L. Interleukin-17 production in central nervous system infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 2008, 172:146-155. 10.2353/ajpath.2008.070690, 2189615, 18156204.
56. Du L, Bayir H, Lai Y, Zhang X, Kochanek PM, Watkins SC, Graham SH, Clark RS. Innate gender-based proclivity in response to cytotoxicity and programmed cell death pathway. The Journal of Biological Chemistry 2004, 279:38563-38570. 10.1074/jbc.M405461200, 15234982.
57. Ortona E, Margutti P, Matarrese P, Franconi F, Malorni W. Redox state, cell death and autoimmune diseases: a gender perspective. Autoimmunity Reviews 2008, 7:579-584. 10.1016/j.autrev.2008.06.001, 18599384.
58. Hansen JM, Go YM, Jones DP. Nuclear and mitochondrial compartmentation of oxidative stress and redox signaling. Annual Review of Pharmacology and Toxicology 2006, 46:215-34. 10.1146/annurev.pharmtox.46.120604.141122, 16402904.
59. Song JJ, Lee YJ. Differential role of glutaredoxin and thioredoxin in metabolic oxidative stress-induced activation of apoptosis signal regulating kinase 1. Biochemical Journal 2003, 373:845-53. 10.1042/BJ20030275, 1223534, 12723971.
60. Kim SH, Oh J, Choi JY, Jang JY, Kang MW, Lee CE. Identification of human thioredoxin as a novel IFN-gamma-induced factor: mechanism of induction and its role in cytokine production. BMC Immunology 2008, 9:64. 10.1186/1471-2172-9-64, 2596082, 18983687.
61. Pellegrini P, Contasta I, Berghella AM, Del Beato T, Casciani CU, Adorno D. The TH1 and TH2 cytokine network in healthy subjects: suggestions for experimental studies to create prognostic and diagnostic indices for biotherapeutic treatments. Cancer Biother Radiopharm 2000, 15:267-78. 10.1089/108497800414365, 10941534.
62. Sprott RL. Biomarkers of aging and disease: introduction and definitions. Exp Gerontol 2010, 45:2-4. 10.1016/j.exger.2009.07.008, 19651201.
63. Barker PE, Murthy M. Biomarker Validation for Aging: Lessons from mtDNA Heteroplasmy Analyses in Early Cancer Detection. Biomark Insights 2009, 4:165-79. 2796862, 20029650.
64. Vasto S, Carruba G, Lio D, Colonna-Romano G, Di Bona D, Candore G, Caruso C. Inflammation, ageing and cancer. Mech Ageing Dev 2009, 130:40-5. 10.1016/j.mad.2008.06.003, 18671998.
65. Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp Gerontol 2004, 2004(39):687-699.