Inflammation IL-6 dan hsCRP and Prostate Hyperplasia on Ab-Ob

69 0,71 0,15-3,62 pgdL and 1,45 0,3-13,5 vs 1,00 0,2-9,2 mgL. This result may be cause by mean in case group or control group than have normal IL-6 level. Interleukin and acute phase reactant levels very fluctuate in plasma so that can’t describe reality condition. In other hand condition that may be affect sample in this research was taken operative patient so that cytokines load will be decrease parallel with decrease of prostate mass after hyperplasia. Cross sectional study by Saadi et al., find that if hsCRP and IL-6 the highest level was in BPH group with LUTS if compare with BPH group alone or with normal people This study involve 56 sample that divided by 3 group, BPH+LUTS group, BPH alone and healthy people. hsCRP level mean for each group was 10,04±1,58; 5±0,36; 2,8±0,5 mgL with p0,001. IL-6 level mean was 14,56±1,1; 8,82±0,93; 12,6±0,82 with p0,001 Saadi et al., 2012. Other study by Hung et al., find there is significant correlation between hsCRP to prostate volume Hung et al., 2014. This study was a cross sectional with high sample size that involve 853 sample. Mean of hsCRP level on subject base characteristic was 3,1±0,43 mgdL, significantly correlated to IPSS score with correlation coefficient r=0,151, p0,001. If we compare our research, we find that a very low level of IL-6 on Ab-OB group with prostate hyperplasia, even with range between 0,25-3,72 mgdL. There is a high influence to insignificant results of IL-6 and hsCRP that increase risk of BPH on Ab-OB although conceptually and theoretically inflammation have a central role in correlation between fibrosis and prostate hyperplasia. In this research we only find that there is a tendency of IL-6 and hsCRP higher than case group if compare with control group. IL-6 and hsCRP level in our research lower than other study above. Several epidemiologic study show that 25 of malignancy correlated with chronic inflammation and 15 death case from cancer caused by inflammation Hsing, 2007; Burton et al., 2007. Release of inflammation mediator that chronically happen and excessive theorically considered cause increase initiation, 70 promotion and progression of tumor Lehrer et al., 2005; Bruton et al., 2007. On obesity, adipose tissue in chronic inflammation condition, which have important role to insulin resistance, dyslipidemia accuracy and also other comorbidity disease such as cardiovascular disease and cancer. This inflammation is being mark with elevation CRP level, IL-6, IL-8, MCP- 1 and TNFα. Mechanism that explained how obesity induced chronic inflammation can increase prostate hyperplasia include: ii elevation proinflammation mediator production such as cytokine, chemokine, ROI, ii increase oncogene expression, COX-2, 5- LOX, and MMPs, iii elevation pro inflammation transcription factor, such as NF- κB, STAT3, AP-1. Infiltration from chronic inflammation often happen at peripheral side of the prostate. Inflammation described with PMN infiltration, cytokine and chemokine including CRP. CRP also release from adipose tissue. CRP is acute phase protein that secreted from liver and unspecific marker for inflammation, infection, tissue damage. This inflammation mediator will inducedother proinflammation transcription factor such as NF- κB and iNOS. NF- κB was strong inducer from gene that related to anti apoptosis activity and gene that arrange cell cycle life cyclin D1. NF- κB and iNOS are very important role in cellular immune activity, had antimitogenic and antiapoptosis effect. Activation NF- κB and iNOS by proinflammtion cytokine will induce tumour cell initiation and progressivity. Proinflammation cytokine will also induce PMN to produce ROS and RNS, which next induce DNA mutation and form tumor. Infection and releasing proinflammation cytokine caused by chronic inflammation on prostate will cause lesion like PIA, whereas the focal atrophy on prostate tissue with epithel tissue proliferation and inflammation cells infiltration. In this research there is no prove that Ab-Ob with high level of CRP and IL-6 level have more risk to prostate hyperplasia if compared with Ab-Ob without prostate hyperplasia. 71

6.4 Insulin resistence increase risk of Prostate Hyperplasia via increase of IGF-1 on Ab-Ob

In this research find that if HOMA-IR and IGF-1 level was high both have role to increase risk of prostate hyperplasia in abdominal obesity. Logistic regression multivariate analysis show that insulin resistance assessed from high level of HOMA-IR and IGF-1 state the high HOMA-IR increase risk of prostate hyperplasia with OR=4,18 CI: 1,15-15,00, p=0,03; High level of IGF-1 increase risk of prostate hyperplasia with OR=4,93 CI: 1,76-13,28, p=0,002. If further analysis was done, role of insulin resistance HOMA-IR to predict and increase risk prostate hyperplasia event on Ab-Ob show y=-0,89+1,43HOMA-IR+1,59IGF-1. Probability for prostate hyperplasia event was p=11+e -y , when e was natural number with value 2.7. HOMA-IR value 1 when level was 2.7, IGF-1 value 1 when level was 150ngml. All variable value o in y equation when value cut off points. So that if we get IGF-1 150ngml and HOMA-IR 2.7 then probability to undergo prostate hyperplasia is 89. Result of this research prove that insulin resistance that assessed from HOMA-IR and IGF-1 level together have role as risk factor to prostate hyperplasia on abdominal obesity. This result was supported by several hypothesis and correlated theory that we try to analysis and synthesize reckon that there is no research about insulin resistance and IGF-1 within increase risk of prostate hyperplasia on Ab-Ob. Another research that related to obesity, insulin resistance, IGF-1 already explained in chapter 6.1, 6.2 and 6.3 Central role of Ab-Ob within induce insulin resistance will increase insulin level that related to mitogenic effect and growth promoting effect significantly. We know insulin have role as growth factor that increase risk of prostate hypertrophy via activation of IGF system so that can increase production and bioavailability of IGF-1 Giovannuci, 2003. Ab-Ob relates with increased level of IGF-1 to GH and increase GH binding protein Gleeson et al., 2005. Increase expression of GH receptor can describe suppression decrease to 72 IGF-1 level. IGF-1 level comparable to abdomen fat accumulation on Ab-Ob Lukanova et al., 2003. A theory that still in hypothesis describe if insulin level increase as a result of insulin resistance will decrease IGFBP-1 so that will increase bioavailability of free IGF-1 in the blood. So, IGFBP-1 level can be summarize have reverse relation to insulin level and intraabdomen fat count. In this study, from path analysis was found relationship pattern that describe insulin resistance pathophysiology framework HOMA-IR, IGF-1 to prostate hyperplasia. There is a significant relationship between HOMA-IR with prostate hyperplasia CR=3,64; p0,001, total effect 44, direct effect 31, and indirect effect 13. From this analysis was also found significant relationship between HOMA-IR with IGF-1 CR=4,61; p0,001, direct and indirect effect 379. Also found a direct relationship between IGF-1 to prostate hyperplasia CR=3,19; p=0,001, direct effect 3. Therefore can be conclude that HOMA-IR and IGF-1 have significant effect to prostate hyperplasia and indirect relationship between HOMA-IR to prostate hyperplasia through increase of IGF-1. This research result is consistent with Nam et al. In this study was found that fasting insulin level on sample with obesity is significantly higher if compared with sample without obesity Nam et al., 1997. On the sub analysis was found positive relationship between free IGF-1 with fasting insulin r=0,058, p=0,001. Insulin and IGF work through 2 mechanism that is work in cell level as a growth factor and as a hormone that regulate growth and energy metabolism. IGF has an important role in cellular life, regulate growth and development of cell, proliferation activation, cell differentiation and transformation, and inhibit apoptosis Baserga et al., 2003; Renehan et l., 2006; McKee et al., 2009; Lima et al., 2010. Structurally, IGF-1R mimics insulin receptor, present 50 homolog between that 2 receptor. This condition possibly make cross bound between IGF-1 and insulin on that receptor, so that other than metabolic role of insulin, this theory