Comparative Biochemical Study of Interleukin -35 and Some Sex Hormones in MS Female Patients with Duration of the Disease* Ali K. Baden Bushra H. Ali drbushra750@yahoo.com Dept. of Chemistry/College of Education for Pure Science(Ibn Al-Haitham) / University of Baghdad Received in : 9 September 2013 , Accepted in :24 September 2013 Abstract Multiple sclerosis (MS) is a chronic disorder of the central nervous system (CNS) characterized by autoimmune inflammation, demyelination, and axonal damage. The present study aimed to shed a light on the contribution of interlukin-35 and its relation to some sex hormones in the pathogenesis of multiple sclerosis. Sixty six female patients with age range (20-40) years were taken from Baghdad Teaching Hospital through the period from Nov. 2012 to –April 2013 and 20 apparently healthy subject as control group matched age as group G1. The patients were divided into three groups depending on duration of MS diseases G2 from 3 months to 2 years, G3 from 2 years to 4 years, G4 from 4 years to 10 years and more. Investigations included estimation of serum levels of Interlukin-35 (IL-35), Testosterone (TEST), Progesterone (PROG), follicle stimulating hormone (FSH), luteinizing hormone (LH) and Prolactin (PRL). Serum IL-35 levels were significantly higher in MS patients as compared with control subject, also significant increase appeared in TEST levels in G3 compared to control in for MS female patients. No significant differences were found between PROG and FSH with duration also non-significant difference levels G2 compared to G1 in LH, on the other hand a significant increase levels for LH in G3 and G4 compared to control subject , a significant difference in prolactin levels for G2 and G4, but non-significant difference for G3. From this study a conclusion was drawn, that evaluation of concentration of a new super family cytokines IL-35 can be considered as a clinical biomarker in multiple sclerosis female patients. This finding may indicate that MS might influence cytokine e.g. interleukin-35 production in these patients. Keywords : Interleukin-35- Multiple Sclerosis- Steroid hormones *This paper is part of MSc thesis of the first author 267 | Chemistry @a@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@Ü‹127@@ÖÜ»€a@I1@‚b«@H2014 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (1) 2014 mailto:drbushra750@yahoo.com Introduction Multiple sclerosis (MS) is a chronic disorder of the central nervous system (CNS) characterized by autoimmune inflammation, demyelination, and axonal damage [1,2]. MS, also known as '' disseminated sclerosis '' or ''encephalomyelitis disseminata'', is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as broad of signs and symptoms [3] . The etiology of MS remains elusive; however, it is assumed that both a complex genetic background and environmental factors contribute to disease manifestation [4]. The clinical course of MS classified into Relapsing-remitting MS (RR-MS), Secondary Progressive MS (SP-MS), Primary Progressive MS (PP-MS) and Progressive-relapsing MS (PR-MS) [5]. Regulatory treg cells use a broad range of mechanisms to suppress immunity, including suppressive cytokine such as IL-10, IL-35, and Transforming growth factor beta (TGF-β) [6]. IL-35 belongs to IL-12 family of cytokines. IL-35 (composed of p35 and EBI3) is distinct from other family members in that it is produced by Treg cell populations and is suppressive. In vitro and in vivo, IL-35 has two known biological effects: suppression of the proliferation of conventional T cells, and the conversion of naïve T cells into a strongly suppressive induced Treg cell population, called 'iTr35' cells; which function in via IL-35 [7]. Steroid hormones are crucial substances that mediate a wide range of vital physiological functions of the body these protective effects are thought to be mediated by testosterone's immunomodulatory properties such as decreasing the production of pro-inflammatory cytokines TNFα and IL-1β by macrophages [8] and monocytes [9] as well as increasing production of the anti-inflammatory cytokine IL-10 by T cells [10]. Several in vitro studies have shown that testosterone can also be more directly neuroprotective [11]. It is likely that the immunomodulatory, anti-inflammatory and neuroprotective actions of testosterone contribute to this effect [12]. Prolactin (PRL) has an important role in the innate and adaptive immune-response, by regulating the maturation of CD4- CD8- thymocytes toCD4+ CD8+ T cells via IL-2 receptor expression [13]. There is a correlation between PRL level and the number of B and CD4+ T lymphocytes [14]. PRL changes Th1 and Th2 type cytokine production. PRL up-regulates IL-6 and INFγ production and has an immune regulatory role on IL-2level [15–17]. In addition, Hyperprolactinemia (HPRL) affects dendritic cell (DC) maturation, skewing DC function from antigen presentation to pro-inflammatory phenotype with increased interferon α production [18]. (HPRL) have been described in many autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis(RA), the organ specific autoimmune-diseases associated with HPRL including multiple sclerosis (MS) [19]. Aim of the study The present study aimed to shed a light on the contribution of interleukin-35 and its relation to some sex hormones in the pathogenesis of multiple sclerosis. Methods The present study was performed on a group of 66 female patients attending from Baghdad Teaching Hospital in MS unit during Nov.2012 to April 2013 .They were diagnosed by physician at the hospital using Magnetic Resonance Imaging ( MRI) examination .The patients were divided into three groups depending on duration of MS diseases (G2) from 3monthes to 2years ,(G3)from 2yers two four years, (G4) from 4years to 10 years and more . In addition, to group (G1) of 20 healthy were enrolled in the study as a control group. Five ml blood were drawn from all subjects enrolled in this study, and kept in plain tubes left to clot at room temperature for 15 min which separated the serum and stored at -20 °C until used to 3500 rpm for 10 min to estimate IL-35 and sex hormones. 268 | Chemistry @a@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@Ü‹127@@ÖÜ»€a@I1@‚b«@H2014 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (1) 2014 Interleukin 35(IL-35) has been estimated by using enzyme Linked Immuno Sorbent Assay (ELISA) technique using the manufacturer instruction as supplied with kit from Cusabio, China, TEST determination by kits supplied from Accu Bind, USA, PROG, FSH, LH and PRL supplied from Human, Germany determinations. Statistical analysis Results were expressed as Mean± SEM. Student-test was used to show the difference between groups variation was considered significant when P-values are ≤ 0.05. The correlation coefficient (r) test is used to describe the association between the different studied parameters. Results Table (1) shows the levels of IL-35,TEST, PROG,FSH,LH and PRL concentration in sera of G1,G2,G3 and G4 for control and patients respectively. The interleukin-35 (IL-35) levels showed a high significant increase (p<0.001) in sera of group 2 (G2) (34.7± 1) pg/ml, group 3 (G3) (35±0.66) pg/ml compared to group 1 (G1) (23.6±0.82) pg/ml, while there was a highly significant decrease (p<0.001) for group 4 (G4) (35.5±0.83) pg/ml compared to group 1 (G1) (23.6±0.82) pg/ml, while a non significant difference (p>0.05) was noticed among the patient groups. Testosterone showed significant increase (p<0.05) in (G3) (2.9±0.38) ng/ml compared to (G1) (0.56±0.04) ng/ml, while it showed no significant difference (p>0.05) in (G4) (1.2±0.34) ng/ml and (G3) (2.9±0.38) ng/ml compared to (G2) (1.6±0.59) ng/ml, also there was a non significant difference (p>0.05) in (G4) (1.2±0.34) ng/ml and (G2) (1.6±0.59) compared to (G1) (0.56±0.04) ng/ml. Progesterone level showed highly significant decrease (p<0.001) for (G3) (5.3±1.2) ng/ml compared to (G1) (0.6±0.08) ng/ml, also there was a significant increase (p<0.05) in (G2) (9.5±2.47) ng/ml compared to (G1) (0.6±0.08) ng/ml, while there was a non significant difference (p>0.05) in (G4) (4.1±1.68) ng/ml compared to (G1) (0.6±0.08) ng/ml, also there was a non significant difference (p>0.05) in (G4) (4.1±1.68) ng/ml and for (G3) (5.3±1.2) ng/ml compared to in (G2) (9.5±2.47) ng/ml. Results of FSH showed a no significant difference in (G4) (6.2±0.76) IU/l, (G3) (4.7±0.7) IU/l, and (G2) (12.08±4) IU/l compared to group 1 (G1) (5±0.35) IU/l, also in (G4) (6.2±0.76) IU/l, (G3) (4.7±0.7) IU/l compared to (G2) (12.08±4) IU/l. While Luteinizing hormone levels showed highly significant increase (p<0.001) in group 3 (G3) (2.6±0.4) IU/l compared to (G1) (11.7±1.31) IU/l, on other hand there was highly significant decrease (G4) (2.9±0.42) IU/l compared to (G1) (11.7±1.31) IU/l, while there was a significant decrease (p<0.05) in (G3) (2.6±0.4) IU/l, and (G4) (2.9±0.42) IU/l compared to (G2) (7±1.87) IU/l, but there was a non significant difference (p>0.05) in (G2) (7±1.87) IU/l compared to (G1) (11.7±1.31) IU/l. Prolactin levels showed significant increase (p<0.05) in (G4) (20.5±4.41) ng/ml compared to (G1) (8.2±0.67) ng/ml, while there was a non significant difference (p>0.05) for (G3) (9.1±1.44)ng/ml and (G2) (13.3±2.62) ng/ml compared to (G1) (8.2±0.67) ng/ml, also there was a non significant difference (p>0.05) in (G4) (20.5±4.41) ng/ml and (G3) (9.1±1.44)ng/ml compared to (G2) (13.3±2.62) ng/ml. Table (2) shows positive correlation for IL-35,PROG,PRL and duration of diseases (r=0.139,0.162 ,0.327 respectively) as well as the positive correlation in G3 for LH (r= 0.021) ,G4 for TEST,FSH,LH and PRL(r=0.046,0.265,0.0841 and 0.026) as shown in figures (1,2,3,4,5) respectively, while there was negative (-ve) correlation in G3,G4 for IL-35 (r=-0.142, -0.178 ) ,G2,G3 for TEST( r=-0.17,r=-0.134),G3,G4,for PROG( r=-0.112,-0.22),G2,G3 for FSHR(r=-0.404,-0.118), G2 for LH(r=-0.283) , G3for PRL(r=-0.092) & duration. 269 | Chemistry @a@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@Ü‹127@@ÖÜ»€a@I1@‚b«@H2014 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (1) 2014 Discussion The results in the present study showed that the serum level of IL – 35 was significantly higher in patients with MS than in healthy control. But other study suggested that MS is a debilitating neuro inflammatory disease that occurs when auto reactive T cells gain entry into the central nervous system (CNS) and destroy myelin-producing oligodendrocytes. T cell-derived cytokines, including Th1, Th17, IL-17 and IFN-γ, are primarily responsible for the disease symptoms that occur when the myelin sheath that insulates the neurons is damaged during MS [20]. Inflammatory dendritic cells (DCs) and macrophages also contribute to disease induction and progression by activating these auto reactive T cells and secreting inflammatory cytokines in the CNS. Recent studies have identified that chemical mediators, interleukin-23 (IL-23) and granulocyte macrophage colony-stimulating factor (GM-CSF), contribute to the autoimmune characteristics of these T cells. Data suggests that absence of these pro-inflammatory signals was sufficient to prevent inflammation in the brain. This suggests that therapeutic strategies directed at blocking the production of inflammatory mediators could be effective for treating MS [21]. Other study provides that IL-35 can be used to induce the conversion of conventional CD4+ T-cells into induced regulatory T-cells that have potent suppressive capacity in vitro and in vivo [22]. These cells have been designated iTr35 cells by the inventors. This approach can be used to generate regulatory T- cells to treat autoimmune and inflammatory diseases, such as (but not limited to) type 1 diabetes, MS, arthritis, asthma and allergic diseases, IBD, etc. The autoimmune diseases involve both genetic and environmental factors and the autoimmune process is characterized by the breakdown of tolerance in subjects with genetic susceptibility, with subsequent target (organ-specific and not) injury, that, in turn, elicits repairing mechanisms. Increasing evidence in the literature suggests an important role of the microenvironment on the immune system activity and of sex steroids in this context. Sex steroids may act at the multiple steps of the autoimmune process with different (and contrasting) effects, depending on the type of the steroid (natural or synthetic), the concentration and co-presence of the ligands and the binding to their specific receptors. Regarding the effectors of the immune system, different actions of sex steroids depend on the type of immunocytes involved (with final stimulatory or inhibitory actions). To complete the scenario, sex steroids may influence the whole process through multiple, contrasting and time-dependent pathways, for instance, modulating the autoimmune destroying process and/or stimulating the reparation. Increasing evidence in the literature indicates an immunomodulatory role of sex steroids in the pathogenesis of autoimmune diseases. The results of the clinical trials will give the basis in order to better define the use of sex steroids in combination with current therapeutic drugs in autoimmunity [23]. Sex steroid receptor modulating drugs are a promising class of therapeutic agents that will provide new approaches in these pathologies. As far as to our knowledge, this is the first in the field at IL- 35 and its relation to steroid hormones in MS patients. References 1. Rossalind , C. and Kalb,R.L. (2012) Multiple sclerosis: The questions you have the Answers you need, 5th Ed. Bradford& Bigelow. 2. Manual, C.; and Samia, J.K. (2012) Immunopathgenesis of multiple sclerosis. J. Clinically immunology. 142(1):8-12. 3. Compston, A. and Coles, A. (2008) Multiple sclerosis, J, Lancet. 372 (9648): 1502–17. 4. Benjamen, W.; Richard, N. and Omer, M. (2012) Multiple Sclerosis. J. Med. 40(10):523- 528. 5. Confavreux, C. and Vukusic, S. (2006) Natural history of multiple sclerosis: a unifying concept. J. Brain, 129 (pt 3): 606-16. 270 | Chemistry @a@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@Ü‹127@@ÖÜ»€a@I1@‚b«@H2014 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (1) 2014 6. Mattson,D.; Petrie, M .and Srivastava, D.K. (1995) Multiple Sclerosis: Sexual dysfunction and its responses to medications. J. Arch Neurol. 52(9):862-868. 7. Goodman, A.D.; Brown, T.R.; Krupp, L.B. (2009) Sustained-release oral fampridine in multiple sclerosis: a randomized, double-blind, controlled trial. J. Lancet. 373: 732-738. 8. Neema, M.; Stankiewicz, J. and Arora, A. (2007). MRI In multiple sclerosis: what inside the toolbox?, J. Neurotherapeutics. 4:602-617. 9. Bruck, W.; Bitsch, A, and Kolenda, H. (1997) Inflammatory central nervous system demyelination: correlation of MRI findings with lesion pathology. J. Ann. Neurol. 42:783- 793. 10. Fisher, E.; Chang, A. and Fox, R.J. (2007). Imaging correlates of axonal swelling in chronic multiple sclerosis brains. J. Ann Neurol. 62:219-228. 11. Van, W.; Lycklama, A .and Jongen P.J. (2001) Hypointense lesions on T1-weighted spin- echo magnetic resonance imaging: relation to clinical characteristics in subgroups with multiple sclerosis. J. Arch. Neurol. 58:76-81. 12. Ulf, Z.; Mathias ,W. and Elke, H. (2012) Development of biomarkers for multiple sclerosis as a neurodegenerative disorder. J. Progress in Neurology Sci. 95:670-685. 13. Bettelli, E.; Carrier, Y.; Gao,W.; Korn, T.and Strom, TB. (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. J. Nature. 441(7090):235-8. 14. Siffrin, V.; Radbruch, H.; Glumm, R.; Niesner, R.; Paterka, M. and Herz, J. (2010) In vivo imagingof partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. J. Immunity. 33(3):424-3. 15. Mosmann, T.R.; Cherwinski, H. and Bond, M.W. (1986) Two types of murine helper T cell clone: I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol.136(1):2348–2357. 16. Johnson, A.J.; Suidan, G.L. and McDole, J. (2007) The CD8 T cell inmultiple sclerosis: suppressor cell or mediator of neuropathology, J. Int Rev Neurobiol. 79 :73–97. 17. Skulina, C.; Schmidt, S.; Dornmair, K. and Babbe, H, (2004) Multiple sclerosis: brain- infiltrating CD8+ T cells persist as clonalexpansions in the cerebrospinal fluid and blood. J. Proc Natl Acad Sci. 101:2428–2433. 18. Stromnes, I.M.; Cerretti, L.M.and Liggit D.( 2008) Differential Regulation of central nervous system autoimmunity by Th1 and T(H17) cells. J. Nat Med. 14(3): 337-42. 19. Brennan, F. and Feldmann, M. (2000) Cytokines networks. In: Balkwill F (ed.), the cytokine network, Oxford University Press, New York.pp 49-70. 20. Howard, L.W. and James, M.S. (2012) Multiple Sclerosis Diagnosis and Therapy A John Wiley & Sons, Ltd.pp 18-21. 21. Jock, M.; Carlos S.S. and Nancy .H.( 2013) A Guide for the newly diagnosed of Multiple Sclerosis, 4th Ed. Domes Medical Publishing, LLC. 15-6. 22. Zhao, N.W. (2010) Interleukin (IL)-35 is raising our expectations. J. Rev Med Chile. 138: 758-766. 23. Martocchia, A.; Stefanelli, M.; Cola S. and Falaschi, P. (2011) Sex Steroids in Autoimmune Diseases. J. Curr Top Med Chem. 11: 1668-83. 271 | Chemistry @a@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@Ü‹127@@ÖÜ»€a@I1@‚b«@H2014 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (1) 2014 Table (1): Levels of IL-35, Testosterone, Progesterone, Prolactin, FSH, and LH in sera of the four studied groups. Studied Groups Parameter Control (G1) mean±SEM MS (G2) mean±SEM MS (G3) mean±SEM MS (G4) mean±SEM G2 vs G1 G3 vs G1 G4 vs G1 G3 vs G2 G4 vs G2 IL-35Pg/ml 23.6±0.82 34.7±1 35±0.66 35.5±0.83 HS HS HS NS NS TEST ng/ml 0.56±0.04 1.6±0.59 2.9±0.38 1.2±0.34 NS S NS NS NS PROGng/ml 0.6±0.08 9.5±2.47 5.3±1.2 4.1±1.68 S HS NS NS NS FSH IU/l 5±0.35 12.08±4 4.7±0.7 6.2±0.76 NS NS NS NS NS LH IU/l 11.7±1.31 7±1.87 2.6±0.4 2.9±0.42 NS HS HS S S PRL ng/ml 8.2±0.67 13.3±2.62 9.1±1.44 20.5±4.41 NS NS S NS NS P values< 0.05 considered significant (S) P values< 0.001 considered highly significant (HS) P values>0.05 considered non- significant (NS) Table (2): Correlation analysis between biochemical parameters among three studied groups. Group2 (G2) MS Group 3 (G3) MS Group 4 (G4) MS IL-35&YEARS r 0.139 -0.142 -0.178 p P<0.05 P<0.05 P<0.05 TEST& YEARS r -0.170 -0.134 0.046 p P<0.05 P<0.05 P<0.05 PROG& YEARS r 0.162 -0.112 -0.220 p P>0.05 P>0.05 P>0.05 FSH& YEARS r -0.404 -0.118 0.265 p p>0.05 p>0.05 p>0.05 LH& YEARS r -0.283 0.021 0.0841 p p>0.05 P<0.05 P<0.05 PRL& YEARS r 0.327 -0.092 0.0260 p P<0.05 p>0.0 P<0.05 272 | Chemistry @a@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@Ü‹127@@ÖÜ»€a@I1@‚b«@H2014 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (1) 2014 Fig. (1): Correlation between IL-35 and duration of disease in years Fig. (2): Correlation between Testosterone and duration in years. G2 y = 0.2056x + 33.438 R² = 0.0196 r= 0.139 G3 y = -0.1378x + 35.91 R² = 0.0202 r= -0.142 G4 y = -0.2172x + 36.908 R² = 0.0317 r=-0.178 0 5 10 15 20 25 30 35 40 45 0 2 4 6 8 10 12 14 IL-35 YEARS series1= G2 series2=G3 series3=G4 Series1 Series2 Series3 G2 y = -0.1488x + 2.6324 R² = 0.029 r= -0.170 G3 y = -0.1641x + 3.9455 R² = 0.018 r= -0.134 G4 y = 0.024x + 1.1351 R² = 0.0022 r=0.046 0 2 4 6 8 10 12 14 0 5 10 15 TEST ng/ml YEARS series 1=G2 series1=G3 series3=G4 Series1 Series2 Series3 Linear (Series1) 273 | Chemistry @a@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@Ü‹127@@ÖÜ»€a@I1@‚b«@H2014 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (1) 2014 Fig.(3):Correlation berween Progesterone and duration of diseases in years Fig .(4): Correlation between FSH and duration of diseases in years. G2 y = 0.5913x + 5.889 R² = 0.0264 r=0.162 G3 y = -0.2008x + 6.6221 R² = 0.0126 r= -0.112 G4 y = -0.5459x + 7.4836 R² = 0.0485 r= -0.220 0 5 10 15 20 25 30 35 40 45 0 5 10 15 PROG ng/ml YEARS series1=G2 series2=G3 series3=G4 Series1 Series2 Series3 Linear (Series1) Linear (Series2) G2y = -1.2196x + 19.737 R² = 0.0418 r= -0.204 G3y = -0.1241x + 5.5547 R² = 0.014 r= -0.118 G4y = 0.2989x + 4.3485 R² = 0.0703 r= -0.265 0 10 20 30 40 50 60 70 80 0 5 10 15 FSH IU/l YEARS series1= G2 series2=G3 series3=G4 Series1 Series2 Series3 Linear (Series1) 274 | Chemistry @a@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@Ü‹127@@ÖÜ»€a@I1@‚b«@H2014 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (1) 2014 Fig.(5): Correlation between LH and duration of diseases in years. Fig .(6):Correlation berween PRL and duration of diseases in years. G2 y = -0.7854x + 11.936 R² = 0.0806 r= -0.283 G3y = 0.013x + 2.5524 R² = 0.0005 r=0.021 G4y = 0.0526x + 2.593 R² = 0.0071 r= 0.084 0 5 10 15 20 25 30 35 0 5 10 15 LH IU/l YEARS series1=G2 series2=G3 series3=G4 Series1 Series2 Series3 G2 y = 1.2571x + 5.4793 R² = 0.1073 r= -0.283 G3 y = -0.1972x + 10.363 R² = 0.0086 r= 0.021 G34y = 0.1682x + 19.533 R² = 0.0007 r= 0.026 0 10 20 30 40 50 60 70 80 90 0 5 10 15 PRL ng/ml YEARS series1=G2 series2=G3 series3=G4 Series1 Series2 Series3 Linear (Series1) 275 | Chemistry @a@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@Ü‹127@@ÖÜ»€a@I1@‚b«@H2014 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (1) 2014 عند وبعض الھرمونات الجنسیة 35 -دراسة كیمو حیویة مقارنة لال نترلیوكین مریضات التھاب االعصاب المتعدد مع مدة من المرض علي كاظم بدن بشرى حمید علي جامعة بغداد /) ابن الھیثم( كلیة التربیة للعلوم الصرفة /قسم الكیمیاء 2013أیلول 24، قبل البحث في : 2013أیلول 9استلم البحث في : الخالصة تصلب االعصاب المتعدد ھو اضطراب في الجھاز العصبي المركزي ویوصف بانھ احد امراض المناعة الذاتیة وعالقتھ 35-االلتھابیة وفقدان المایلین وتحطم المحاور .ھذه الدراسة تھدف الى تسلیط الضوء على مساھمة االنترلیوكین ) مریضة 66ض تصلب االعصاب المتعدد . أجریت التجربة على (مع بعض الھرمونات الجنسیة االساسیة في نشوء مر وكذالك 2013ألى أبریل 2012) سنة من مستشفى بغداد التلعیمي للمدة من نوفمبر 40-20بمعدل عمر یتراوح بین ( على مجموعة السیطرة بالفئة العمریة نفسھا وعدت مجموعة أولى. قسمت الحاالت المرضیة على ثالث مجامیع باالعتماد أشھر إلى سنتین مجموعة ثانیة، والمدة من سنتین 3مدة االصابة بمرض التصلب العصبي المتعدد ، حیث أعتبرت المدة من سنوات أو اكثر مجموعة رابعة. تضمن التشخیص تقدیر مستوى 10سنوات إلى 4سنوات مجموعة ثالثة، والمدة من 4إلى فضال عن LHالبروجیستیرون ، والھرمون المحفز للجریبات ، و ھرمون و التستوستیرون، وھرمون 35-أالنترلیوكین عند مریضات التصلب العصبي التعدد 35-ھرمون البروالكتین. وأتضح وجود أرتفاع جوھري بمستوى االنترلیوكین و التستوستیرون عند مریضات التصلب العصبي 35-مقارنة باالصحاء و ھذه الحقائق وجدت في مستوى أالنترلیوكین لبروجیستیرون والھرمون المحفز للجریبات خالل مدة المرض المتعدد. لوحظ عدم وجود اختالف جوھري بین ھرمون ا خالل المدة المرضیة للمجموعة الثانیة، فضال عن وجد فرق جوھري في LHوكذالك لم یالحظ أختالف جوھري لھرمون مھم مستوى ھرمون االتینزنك في المجموعتین الثالثة والرابعة خالل مدة المرض ،أما ھرمون البروالكتین فوجد أختالف بالنسبة الى المجموعتین الثانیة و الرابعة على عكس المجموعة الثالثة التي لم یوجد بھا فرق جوھري. من ھذه الدراسة التي یمكن أن یعد دالة كیموحیویة للمصابات بمرض التصلب 35-أجریت نستنتج بأن أرتفاع مستوى تركیز أالنترلیوكین الموجود 35-مرض التصلب العصبي المتعدد یتأثر بالسایتوكین مثل أالنترلیوكین العصبي المتعدد. وتبین ھذه النتیجة أن عند تلك المریضات. ، التصلب العصبي المتعدد، الھرمونات السترویدیة. 35-أنترلیوكین الكلمات المفتاحیة: 276 | Chemistry @a@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@ÚÓ‘Ój�n€a@Î@Úœäñ€a@‚Ï‹»‹€@·rÓ:a@Âig@Ú‹©@Ü‹127@@ÖÜ»€a@I1@‚b«@H2014 Ibn Al-Haitham Jour. for Pure & Appl. Sci. Vol. 27 (1) 2014