Effects of Interleukin Families Polymorphisms on Systemic Lupus Erythematous Disorder: Focus on Interleukin-1

4872 words (19 pages) Full Dissertation in Full Dissertations

06/06/19 Full Dissertations Reference this

Disclaimer: This work has been submitted by a student. This is not an example of the work produced by our Dissertation Writing Service. You can view samples of our professional work here.

Any opinions, findings, conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of UK Essays.

Effects of Interleukin Families Polymorphisms on Systemic Lupus Erythematous Disorder: Focus on Interleukin-1

Abstract

Systemic lupus erythematous (SLE) disease increases the activity of B cells and production of antibodies against tissue antigens. This disease damages on many tissues and organs such as joints, kidneys, heart and nervous system. The exact cause of SLE is unknown, but it is suggested that genetic background plays an important role in lupus pathogenesis. Many studies suggested that interleukins play important role in progression of SLE. Interleukins are a group of cytokines, which secreted by T helper cells, monocytes, macrophages and B cells, and involved in growth and differentiation of T and B cells. The expression levels of interleukins are controlled by genetic background. Furthermore, some polymorphisms increase or decrease the expression of interleukins. Understanding these factors increase our information about the SLE. Therefore, in present study we reviewed the roles of eight important interleukins polymorphisms and their effects on SLE pathogenic.

Keyword: Interleukin-1, Cytokines, Systemic Lupus Erythematous

1. Introduction

Systemic lupus erythematous (SLE) is a chronic human autoimmune disease which affects various body organs in the human. This disease is created with increased activity of B cells and production of antibodies against endogenous antigens in body. Accumulation of antibodies in tissues and organs plays a key role in clinical signs of SLE (1, 2). Lupus can have an impact on many organs such as kidneys, heart and nervous system. The joints affected more in SLE type and the skin affected much more in all types of lupus (3, 4).

The prevalence of lupus in different populations is 20 to 150 cases per 100,000 individuals around the world (2). Also the disease in women of reproductive age is about 9 times more frequent than men, and its prevalence is variable in race, ethnicity, geographic and social and economic status. This disease is not common in children and about 20% of the patients are children less than 15 years (5).

The exact causes of this disease are still unknown, but genetic and environmental factors play an important role in the lupus pathogenesis (6). The genetic basis of lupus is very complex and determines the number of involved genes in different stages of disease is difficult (7). It seems that this disease is created due to the loss of the body’s tolerance to insider’s antigens and then production of antibodies against the cell’s nucleus (8, 9). Generally, lupus was classified in four groups including; discoid lupus, drug-induced lupus, neonatal lupus and systemic lupus erythematous (10).

Interleukins (IL) are a group of cytokines, which secreted mostly by T helper cells, monocytes, macrophages, dendritic cells, natural killer cells and cell B. The interleukins mainly involved in the growth and differentiation of T and B cells and activate natural killer cells. Several studies showed that inflammatory interleukin genes play an important role in creation of SLE. These interleukins include; interleukin 1 (11), interleukin 1 beta (12), interleukin 4 (12), interleukin 6 (13), interleukin 7 (14), interleukin 10 (13), interleukin 21 (15), interleukin 19 (16), interleukin 27 (17), interleukin 31 (18) and interleukin 32 (19).

Recognizing of these interleukins increases our information about the SLE disorder and leads to development of novel treatment methods and early diagnosis. In the present review the roles of inflammatory interleukin genes and especially the Interleukin 1 gene family were studied in creating the SLE disease.

2. Interleukins involved in Systemic Lupus Erythematous

The cytokines are secreted by cells which involved in immune systems, such as T cells and other immune response cells. According to the types of T cell, some of the cytokines play inhibitory roles and some other play excitatory roles. One of the most important issue is the balance between Th1/Th2 cytokines, which loss of this balance lead to SLE. Yet, there is not comprehensive information about the relationship between Th1 and Th2 levels; however, it is clear that increasing levels of Th2 is important in progression of SLE. On other hands, reducing levels of Th1 involved in progression of SLE. There are many important Th1 and Th2 cytokines, which involved in pathogenesis of SLE, such as IL-12, IL-4, IL-10 and IL-6 (4, 20, 21).

Production of interleukins can be controlled by genetic factors, and it seems that some polymorphisms can lead to increase or decrease the expression of interleukin genes, thereby increase the susceptibility to certain diseases (22). Thus, different studies reported significant association between interleukins and SLE, which will be described below.

2.1. Interleukin 23 (IL-23)

It is believed that the IL-23 is an important factor in the pathogenesis of autoimmune diseases. Recently abnormalities in this cytokine have been reported in the development of SLE. The IL-23 is able to stimulate TCD4 for production of pro-inflammatory cytokines such as IL-17 and IFNγ. So, this cytokine plays an important role in progression of SLE. Clinical and pathological signs of SLE nephritis were decreased in defect of IL-23 receptors. Therefore, it appears that IL-23 is an essential factor in damaging the kidneys in SLE patients (23, 24).

2.2. Interleukin 21 (IL-21)

IL-21 is produced from follicular T cells. This cytokine induces differentiation and development of T helper cell, and stimulates the production of antibodies by B cells. Therefore, IL-21 plays an important role in progress of SLE (25). Previous studies showed that plasma levels of IL-21 have increased in patients with SLE.

Variations in the IL-21 gene may lead to change in IL-21 protein, which can alter the susceptibility of individuals to SLE. Several polymorphisms in the IL-21 gene have been identified in association with SLE (26-28). Recently, some studies showed that IL-21 increases inflammatory diseases and autoimmune chronic diseases in human. Also animal studies reported that IL-21 plays an important role in the pathogenesis of SLE, and its serum level in patients was more than healthy persons. In addition, some other studies showed that the polymorphisms of IL-21 and its receptor were associated with susceptibility to SLE (29).

2.3. Interleukin 18 (IL-18)

The IL-18 protein is belongs to IL-1 family and it is in an inactive form, which needs to be cut by caspase-1 to become biologically active form. The IL-18 has many biological function, such as influences on dendritic cells, T lymphocytes and natural killer cells, and is a potent inducer of IFN-A to increase differentiation of Th1 cell (30). Previous studies showed that concentration of IL-18 has increased in patients with SLE. Also some other studies reported that levels of IL-18 was associated with kidney problems in SLE patients (31, 32). Serum levels of IL-18 in SLE patients was more than healthy controls and it was associated with micro-albumin levels in urine (33). In addition, the gene expression of IL-18 has increased in the glomeruli of patients with SLE nephritis (33). Also over-expression of IL-18 causes skin lesions in patients with SLE (34).

2.4. Interleukin 17 (IL-17)

The IL-17 is a pro-inflammatory cytokine, which is well-known as IL-17A and plays an important role in the regulation of inflammation process. In past years, it was identified that six types of IL-17, involved in SLE, such as IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F. This pro-inflammatory cytokines, primarily released by activated T lymphocytes (35, 36). IL-17 significantly leads to proliferation of cell B and production of antibodies. Therefore, elevation of serum IL-17 have been reported in development of SLE disease (23, 24, 37). Recent studies showed that IL-17 releases significantly by lymphocytes T, in patients with SLE (38). In addition, the IL-17 induced adhesion of mRNA molecules and T cells to endothelial cells, in patients with SLE (39).

2.5. Interleukin 10 (IL-10)

It is suggested that IL-10 is involved in suppressing of T cells function, directly. However it seems that, this interleukin plays an important role in increasing B cells activation. IL-10 mainly released by activated macrophages and also at lower values, released by other cell types, such as T cells and keratinocytes (40). The serum levels of IL-10 were increased in SLE patients and it was related with disease activity. This interleukin leads to stimulate the proliferation and differentiation of B cells. Also, the IL-10 affects the expression of Bcl-2 and decreases the apoptosis in B cells. Therefore, it can enhance production of antibody.

Recently, studies showed that injection of IL-10 to mice with SLE leads to increase involvement of kidney in diseases (23, 24, 41). Also, many studies reported that various polymorphisms in the promoter region of the IL-10 gene were associated with SLE (42-44). However, another study has reported no association between IL-10 polymorphisms and susceptibility to SLE in adolescents (45).

2.6. Interleukin 6 (IL-6)

Interleukin 6 (IL-6) was produced by TNF and IL-1. It has pleiotropic effect on many tissues in human. This cytokine secreted by macrophages cells and in lower amounts secreted by mesangial, endothelial and lymphocytes (23). The IL-6 leads to increase the activation and secretion of macrophage, B lymphocyte and immunoglobulin. Also, IL-6 can promote differentiation of Th17 cells, which play important role in many autoimmune diseases. Studies showed that levels of IL-6 increased in the serum and urine in patients with SLE (24). Also many studies reported that this cytokine plays an important role in renal disease in patients with SLE (46).

2.7. Interleukin 4 (IL-4)

The IL-4 gene is an anti-inflammatory cytokine, which produced by Th2 CD4+ cells on the surface of basophils and mast cells (47). The IL-4 protein is a key cytokines, which leads to activation and differentiation of B cells and also involves in development of T cells (48). This cytokine has a cytotoxic effect, which leads to inhibition of nitric oxide synthase, release of dismutase anions by macrophages and some other anti-inflammatory effects. The role of IL-4 is well-known in autoimmune diseases. It seems that the role of IL-4 in the development of SLE depends on genetic background. Some studies showed that the IL-4 gene may be involved in the progress of SLE (49, 50). In our recent study on SLE patients, we demonstrated that IL-4 gene is associated with SLE and may play an important role SLE progression (12).

3. Interleukin 1 family

The interleukin-1 (IL-1) gene cluster is formed from a 430kb region and include encoding genes, such as IL-1α (IL-1A), IL-1β (IL-1B) and receptor antagonist of interleukin-1 (IL-1RN). Many studies showed significant differences in the expression level of IL-1 family between patients with SLE and healthy subjects (11, 22). The IL-1A and IL-1B proteins are pro-inflammatory cytokines and play important role in many biological extensive activities. The IL-1A and IL-1B are binding to the IL-1 receptor and lead to signal transduction and biological effects. In contrast, the IL-1Ra protein is a competitive inhibitor and binding to IL-1 receptors and leads to inhibition of intracellular signaling (51) . It is believed that interfere in balance between these three proteins and their receptors may play important roles in creation of autoimmune diseases.

4. Interleukin 1 and SLE

The IL-1 protein family is a polypeptide include IL-1 alpha (IL-1α), IL-1 beta (IL-1β) and IL receptor antagonist (IL-RA). The IL-1 was located on human chromosome 2 (2q13-21), in 430-kb region, and IL-1α and IL-1β genes are very close together (52). The IL-1α and IL-1β are pro-inflammatory cytokines and involved in many biological activities. Studies suggested that imbalance between IL-1α, IL-1β and IL-RA proteins causes autoimmune response (51). Many studies reported significant relationship in production of IL-1 family with SLE patients (53-55).

Abnormal expression of the IL-1 family members has been involved in progression of SLE, which is revealed since 1983 (56). But so far, many studies have not been performed to investigate the relationship between IL-1 member’s polymorphisms and SLE. In one study performed by Chua et al. (2009), they showed that patients with SLE are susceptible to IL-1β -511C/T polymorphism in Malaysian population; they reported that C allele and its homozygous increases the SLE risk (57). On the other hands, Parks et al. (2004) reported that T allele increases susceptibility of SLE in African Americans population (56). Also Huang et al. (2002), reported no relationship between IL-1β -511C/T polymorphism and SLE in Taiwan population (58). In a similar study Chua et al. (2009), reported a significant association between IL-1β +3954E1/E2 polymorphism in exon 5 and patient with SLE in Malaysian population and E1 allele increases the SLE risk (57). Also this result have seen in patients with SLE Columbian population, but not seen in Chines population (59, 60).

The activity and production of IL-1α and IL-1β are controlled by IL-receptor antagonist (IL-1RA or IL-1RN). The dysregulation in expression of IL-1 by IL-1RA abnormal activity leads to high inflammatory response and cause damage to tissues. The tissues damages are one of the SLE symptoms. Many studies performed to evaluation of association between IL-1RN gene polymorphisms and SLE. The IL-1RA variable numbers tandem repeat -86bp (VNTR 86-bp) polymorphism in intron 2 is relevant with SLE risk (61, 62). Our previous study in association between VNTR 86-bp polymorphism and SLE showed that IL-1RN∗2 allele no association with SLE (11). On the other hands, Blakemore et al. reported association between IL-1RN∗2 allele and SLE susceptibility (62). Also Lian et al. showed that IL-1RN∗2 allele was associated with SLE in Malaysian population (63).

5. Conclusions

In this present study, we have considered some interleukins which play important roles in SLE pathogenesis. Our study showed some cytokines, which have important roles in SLE pathogenesis. SLE is an autoimmune disorder with many heterogeneous symptoms. The main mechanism of this disorder remains unknown. However, many studies suggested that SLE is a multi-factorial disease, which involve genetic, environmental and immunological agents. These factors lead to sensitivity of the body toward antigens; therefore, immunologic responses become out of control in some body tissues and cause damage to these tissues. Many studies performed on SLE patients and SLE animal models showed that over expression of some interleukin families play important roles in the SLE progression. Over expression of some inflammatory interleukins lead to increase of auto reactive B cells, which cause to increase the production of autoantibodies in body. In addition many genetic antigens, which involved in immune response process, TLR signal transduction to IFN type I production and lymphocytes signal transduction are well-known as important factors in pathogenesis of SLE disorder.

Acknowledgements

Declaration of Interest

The authors declare that they have no conflicts of interest.

References

1. Sahebari M, Hatef MR, Rezaieyazdi Z, Abbasi M, Abbasi B. Correlation between serum levels of soluble fas (CD95/Apo-1) with disease activity in systemic lupus erythematosus patients in Khorasan, Iran. Archives of Iranian Medicine. 2010;13(2):135.

2. Crispín JC, Liossis S-NC, Kis-Toth K, Lieberman LA, Kyttaris VC, Juang Y-T, et al. Pathogenesis of human systemic lupus erythematosus: recent advances. Trends in molecular medicine. 2010;16(2):47-57.

3. Fu SM, Deshmukh US, Gaskin F. Pathogenesis of systemic lupus erythematosus revisited 2011: end organ resistance to damage, autoantibody initiation and diversification, and HLA-DR. Journal of autoimmunity. 2011;37(2):104-12.

4. Namazi S, Ziaee V, Rezaei N. The role of cytokines in systemic lupus erythematosis. Tehran University Medical Journal TUMS Publications. 2015;73(6):397-404.

5. Murphy G, Lisnevskaia L, Isenberg D. Systemic lupus erythematosus and other autoimmune rheumatic diseases: challenges to treatment. The Lancet. 2013;382(9894):809-18.

6. Mohammadoo-Khorasani M, Musavi M, Mousavi M, Moossavi M, Khoddamian M, Sandoughi M, et al. Deoxyribonuclease I gene polymorphism and susceptibility to systemic lupus erythematosus. Clinical rheumatology. 2016;35(1):101-5.

7. Horiuchi T, Washio M, Kiyohara C, Tsukamoto H, Tada Y, Asami T, et al. Combination of TNF-RII, CYP1A1 and GSTM1 polymorphisms and the risk of Japanese SLE: findings from the KYSS study. Rheumatology. 2009;48(9):1045-9.

8. Tobón GJ, Izquierdo JH, Cañas CA. B Lymphocytes: development, tolerance, and their role in autoimmunity—focus on systemic lupus erythematosus. Autoimmune diseases. 2013;2013.

9. Ahearn JM, Liu C-C, Kao AH, Manzi S. Biomarkers for systemic lupus erythematosus. Translational Research. 2012;159(4):326-42.

10. Tahernia L, Namazi S, Rezaei N, Ziaee V. Cytokines in systemic lupus erythematosus: their role in pathogenesis of disease and possible therapeutic opportunities. Rheumatology Research. 2017;2(1):1-9.

11. Mohammadoo-Khorasani M, Salimi S, Tabatabai E, Sandoughi M, Zakeri Z. Association of interleukin-1 receptor antagonist gene 86bp VNTR polymorphism with systemic lupus erythematosus in south east of Iran. Zahedan Journal of Research in Medical Sciences. 2013;16(12).

12. Mohammadoo-Khorasani M, Salimi S, Tabatabai E, Sandoughi M, Zakeri Z, Farajian-Mashhadi F. Interleukin-1β (IL-1β) & IL-4 gene polymorphisms in patients with systemic lupus erythematosus (SLE) & their association with susceptibility to SLE. The Indian journal of medical research. 2016;143(5):591.

13. Talaat R, Alrefaey S, Bassyouni I, Ashour M, Raouf A. Genetic polymorphisms of interleukin 6 and interleukin 10 in Egyptian patients with systemic lupus eythematosus. Lupus. 2016;25(3):255-64.

14. Jagodzinski PP, Piotrowski P, Olesińska M. Interleukin-7 receptor Thr244Ile gene polymorphism and the risk of systemic lupus erythematosus. Journal of Medical Science. 2016;85(3):192-6.

15. Ahmed YM, Erfan DM, Hafez SF, Shehata IH, Morshedy NA. The association of single nucleotide polymorphism of interleukin-21 gene and serum interleukin-21 levels with systemic lupus erythematosus. Egyptian Journal of Medical Human Genetics. 2017;18(2):129-36.

16. Lin J, Qin H, Wang Y, Liang J, Xu J. Analysis of interleukin 19 serum levels and single nucleotide polymorphisms in systemic lupus erythematosus. Genetics and molecular research: GMR. 2016;15(2).

17. Paradowska‐Gorycka A, Sowinska A, Stypinska B, Grobelna M, Walczyk M, Olesinska M, et al. Genetic Variants in IL‐12B and IL‐27 in the Polish Patients with Systemic Lupus Erythematosus. Scandinavian journal of immunology. 2016;84(1):49-60.

18. Huang H-T, Chen J-M, Guo J, Lan Y, Wei Y-S. The association of interleukin-31 polymorphisms with interleukin-31 serum levels and risk of systemic lupus erythematosus. Rheumatology international. 2016;36(6):799-805.

19. Wang Y, Zhou B, Zhao Y, Yu X, Liu Y, Zhang L. Association of plasma IL-32 levels and gene polymorphisms with systemic lupus erythematosus in Chinese Han population. Disease markers. 2016;2016.

20. Su D-L, Lu Z-M, Shen M-N, Li X, Sun L-Y. Roles of pro-and anti-inflammatory cytokines in the pathogenesis of SLE. BioMed Research International. 2012;2012.

21. Perl A. Systems biology of lupus: mapping the impact of genomic and environmental factors on gene expression signatures, cellular signaling, metabolic pathways, hormonal and cytokine imbalance, and selecting targets for treatment. Autoimmunity. 2010;43(1):32-47.

22. Tahmasebi Z, Akbarian M, Mirkazemi S, Shahlaee A, Alizadeh Z, Amirzargar AA, et al. Interleukin-1 gene cluster and IL-1 receptor polymorphisms in Iranian patients with systemic lupus erythematosus. Rheumatology international. 2013;33(10):2591-6.

23. Nishimoto N, Kishimoto T. Interleukin 6: from bench to bedside. Nature Reviews Rheumatology. 2006;2(11):619.

24. Cash H, Relle M, Menke J, Brochhausen C, Jones SA, Topley N, et al. Interleukin 6 (IL-6) deficiency delays lupus nephritis in MRL-Faslpr mice: the IL-6 pathway as a new therapeutic target in treatment of autoimmune kidney disease in systemic lupus erythematosus. The Journal of rheumatology. 2010;37(1):60-70.

25. Sarra M, Monteleone G. Interleukin-21: a new mediator of inflammation in systemic lupus erythematosus. BioMed Research International. 2010;2010.

26. Ding L, Wang S, Chen G-M, Leng R-X, Pan H-F, Ye D-Q. A single nucleotide polymorphism of IL-21 gene is associated with systemic lupus erythematosus in a Chinese population. Inflammation. 2012;35(6):1781-5.

27. Leng R-X, Wang W, Cen H, Zhou M, Feng C-C, Zhu Y, et al. Gene–gene and gene-sex epistatic interactions of MiR146a, IRF5, IKZF1, ETS1 and IL21 in systemic lupus erythematosus. PLoS One. 2012;7(12):e51090.

28. Lan Y, Luo B, Wang J-L, Jiang Y-W, Wei Y-S. The association of interleukin-21 polymorphisms with interleukin-21 serum levels and risk of systemic lupus erythematosus. Gene. 2014;538(1):94-8.

29. Webb R, Merrill JT, Kelly JA, Sestak A, Kaufman KM, Langefeld CD, et al. A polymorphism within IL21R confers risk for systemic lupus erythematosus. Arthritis & Rheumatology. 2009;60(8):2402-7.

30. Yap DYH, Lai KN. The role of cytokines in the pathogenesis of systemic lupus erythematosus–from bench to bedside. Nephrology. 2013;18(4):243-55.

31. Wong C, Ho C, Li E, Tam L, Lam C. Elevated production of interleukin‐18 is associated with renal disease in patients with systemic lupus erythematosus. Clinical & Experimental Immunology. 2002;130(2):345-51.

32. Amerio P, Frezzolini A, Abeni D, Teofoli P, Girardelli C, De Pita O, et al. Increased IL-18 in patients with systemic lupus erythematosus: relations with Th-1, Th-2, pro-inflammatory cytokines and disease activity. IL-18 is a marker of disease activity but does not correlate with pro-inflammatory cytokines. Clinical and experimental rheumatology. 2002;20(4):535-8.

33. Calvani N, Richards H, Tucci M, Pannarale G, Silvestris F. Up‐regulation of IL‐18 and predominance of a Th1 immune response is a hallmark of lupus nephritis. Clinical & Experimental Immunology. 2004;138(1):171-8.

34. Wang D, Drenker M, Eiz‐Vesper B, Werfel T, Wittmann M. Evidence for a pathogenetic role of interleukin‐18 in cutaneous lupus erythematosus. Arthritis & Rheumatology. 2008;58(10):3205-15.

35. Sutton CE, Mielke LA, Mills KH. IL‐17‐producing γδ T cells and innate lymphoid cells. European journal of immunology. 2012;42(9):2221-31.

36. Lin AM, Rubin CJ, Khandpur R, Wang JY, Riblett M, Yalavarthi S, et al. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. The Journal of Immunology. 2011;187(1):490-500.

37. Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. The Lancet. 2008;371(9617):987-97.

38. Crispín JC, Oukka M, Bayliss G, Cohen RA, Van Beek CA, Stillman IE, et al. Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. The Journal of Immunology. 2008;181(12):8761-6.

39. Yang J, Chu Y, Yang X, Gao D, Zhu L, Yang X, et al. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis & Rheumatology. 2009;60(5):1472-83.

40. Sabat R. IL-10 family of cytokines. Cytokine & growth factor reviews. 2010;21(5):315-24.

41. Okamoto A, Fujio K, Okamura T, Yamamoto K. Regulatory T-cell-associated cytokines in systemic lupus erythematosus. BioMed Research International. 2011;2011.

42. Lin P-W, Huang C-M, Huang C-C, Tsai C-H, Tsai JJ, Chang C-P, et al. The association of− 627 interleukin-10 promoter polymorphism in Chinese patients with systemic lupus erythematosus. Clinical rheumatology. 2007;26(3):298-301.

43. Sobkowiak A, Lianeri M, Wudarski M, Łącki JK, Jagodziński PP. Genetic variation in the interleukin-10 gene promoter in Polish patients with systemic lupus erythematosus. Rheumatology international. 2009;29(8):921-5.

44. Lin Y, Wan L, Huang C, Sheu J, Chen S, Lin T, et al. IL-10 and TNF-alpha promoter polymorphisms in susceptibility to systemic lupus erythematosus in Taiwan. Clin Exp Rheumatol. 2010;28(3):318-24.

45. Rezaei A, Ziaee V, Sharabian FT, Harsini S, Mahmoudi M, Soltani S, et al. Lack of association between interleukin-10, transforming growth factor-beta gene polymorphisms and juvenile-onset systemic lupus erythematosus. Clinical rheumatology. 2015;34(6):1059-64.

46. Illei GG, Shirota Y, Yarboro CH, Daruwalla J, Tackey E, Takada K, et al. Tocilizumab in systemic lupus erythematosus: Data on safety, preliminary efficacy, and impact on circulating plasma cells from an open‐label phase I dosage‐escalation study. Arthritis & Rheumatology. 2010;62(2):542-52.

47. Pereira VA, Sánchez-Arcila JC, Teva A, Perce-da-Silva DS, Vasconcelos MP, Lima CA, et al. IL10A genotypic association with decreased IL-10 circulating levels in malaria infected individuals from endemic area of the Brazilian Amazon. Malaria journal. 2015;14(1):30.

48. Salimi S, Mohammadoo-Khorasani M, Yaghmaei M, Mokhtari M, Moossavi M. Possible association of IL-4 VNTR polymorphism with susceptibility to preeclampsia. BioMed research international. 2014;2014.

49. Mahmoudi M, Tahghighi F, Ziaee V, Harsini S, Rezaei A, Soltani S, et al. Interleukin‐4 single nucleotide polymorphisms in juvenile systemic lupus erythematosus. International journal of immunogenetics. 2014;41(6):512-7.

50. Yu H, Liu P, Lin Y, Chen W, Lee J, Wang L, et al. Interleukin 4 and STAT6 gene polymorphisms are associated with systemic lupus erythematosus in Chinese patients. Lupus. 2010;19(10):1219-28.

51. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87(6):2095-147.

52. Suzuki H, Takemura H, Kashiwagi H. Interleukin‐1 receptor antagonist in patients with active systemic lupus erythematosus: enhanced production by monocytes and correlation with disease activity. Arthritis & Rheumatology. 1995;38(8):1055-9.

53. Rus V, Atamas SP, Shustova V, Luzina IG, Selaru F, Magder LS, et al. Expression of cytokine-and chemokine-related genes in peripheral blood mononuclear cells from lupus patients by cDNA array. Clinical Immunology. 2002;102(3):283-90.

54. Tayal V, Kalra BS. Cytokines and anti-cytokines as therapeutics—An update. European journal of pharmacology. 2008;579(1):1-12.

55. Scuderi F, Convertino R, Molino N, Provenzano C, Marino M, Zoli A, et al. Effect of pro-inflammatory/anti-inflammatory agents on cytokine secretion by peripheral blood mononuclear cells in rheumatoid arthritis and systemic lupus erythematosus. Autoimmunity. 2003;36(2):71-7.

56. Parks CG, Pandey JP, Dooley MA, Treadwell EL, Clair ES, Gilkeson GS, et al. Genetic polymorphisms in tumor necrosis factor (TNF)-α and TNF-β in a population-based study of systemic lupus erythematosus: associations and interaction with the interleukin-1α-889 C/T polymorphism. Human immunology. 2004;65(6):622-31.

57. Chua K-H, Lau T-P, Tee Z-Y, Tan S-Y, Lian L-H. Genetic polymorphisms of the interleukin-1 beta (IL-1β)-511 and+ 3954 single nucleotide polymorphisms (SNPs) in Malaysian systemic lupus erythematosus (SLE) patients. Journal of Health Science. 2009;55(4):657-62.

58. Yu M-C, Huang C-M, Wu M-C, Wu J-Y, Tsai F-J. Association of TAP2 gene polymorphisms in Chinese patients with rheumatoid arthritis. Clinical rheumatology. 2004;23(1):35-9.

59. Huang C-M, Wu M-C, Wu J-Y, Tsai F-J. Lack of association of interleukin-1ß gene polymorphisms in Chinese patients with systemic lupus erythematosus. Rheumatology international. 2002;21(5):173-5.

60. Camargo J, Correa P, Castiblanco J, Anaya J. Interleukin-1 [beta] polymorphisms in Colombian patients with autoimmune rheumatic diseases. Genes and immunity. 2004;5(8):609.

61. Tarlow JK, Blakemore AI, Lennard A, Solari R, Hughes HN, Steinkasserer A, et al. Polymorphism in human IL-1 receptor antagonist gene intron 2 is caused by variable numbers of an 86-bp tandem repeat. Human genetics. 1993;91(4):403-4.

62. Blakemore AI, Tarlow JK, J Cork M, Gordon C, Emery P, Duff GW. Interleukin–1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus. Arthritis & Rheumatology. 1994;37(9):1380-5.

63. Chai HC, Phipps ME, Chua KH. Genetic risk factors of systemic lupus erythematosus in the Malaysian population: a minireview. Clinical and Developmental Immunology. 2011;2012.

Cite This Work

To export a reference to this article please select a referencing stye below:

Reference Copied to Clipboard.
Reference Copied to Clipboard.
Reference Copied to Clipboard.
Reference Copied to Clipboard.
Reference Copied to Clipboard.
Reference Copied to Clipboard.
Reference Copied to Clipboard.

Related Services

View all

DMCA / Removal Request

If you are the original writer of this essay and no longer wish to have the essay published on the UK Essays website then please:

McAfee SECURE sites help keep you safe from identity theft, credit card fraud, spyware, spam, viruses and online scams Prices from
£29

Undergraduate 2:2 • 250 words • 7 day delivery

Order now

Delivered on-time or your money back

Rated 4.1 out of 5 by
Reviews.co.uk Logo (21 Reviews)

Get help with your dissertation