Pathophysiology Of Anemia Of Chronic Diseases In Lung Cancer Patients

?Objective? To study the relationship between cytokines and anemia of chronic disease(ACD)in lung cancer patients,and the effect of cytokines on the expression of hepcidin gene,in order to explore the pathophysiology of ACD in lung cancer.?Content? ELISA was used to detect the relationship between cytokines and ACD.RT-q PCR was used to detect the effect of EPO,TNF-?,IFN-?,IL-6 and GDF15 on the expression of hepcidin m RNA in Hep G2 cells.?Methods?1.Collection and preservation of serum samples.2.Serum cytokine levels were measured to those lung cancer pacients without anemia,lung cancer pacients with ACD,healthy control population,and lung cancer pacients with ACD treated after EPO combined with intravenous iron.3.Culture of Hep G2 cells with cytokine intervention.4.Total RNA extraction,reverse transcription.5.The expression of hepcidin m RNA in Hep G2 cells was detected by RT-q PCR.?Results?Among lung cancer pacients without anemia(named without anemia group),lungcancer pacients with ACD(named ACD group),and healthy control(named control group),the results show:1.1 EPO of without anemia group was lower than of ACD group(P=0.019).But compared with control group,two groups all had no significant difference(all P > 0.05).1.2 For TNF-?,there was no significant difference between without anemia group with ACD group(P=0.997).But compared with control group,two groups all had significant difference(all P < 0.01).For ACD group,there had no significant difference between before and after treatment(P = 0.71).1.3For IFN-?,there was no significant difference between without anemia group with ACD group(P=0.966),but two groups were all higher than control group(all P < 0.01).For ACD group,there had no significant difference between before and after treatment(P = 0.78).1.4 For IL-6,wihout anemia group was lower than ACD group(P =0.043),and two groups were all higher than control group(all P < 0.05).For ACD group,there had no significant difference between before and after treatment(P=0.412).1.5 For IL-1,there was no significant difference between without anemia group with ACD group(P=0.974),but two groups were all higher than control group(all P < 0.05).For ACD group,there have no significant difference between before and after treatment(P=0.911).1.6 For GDF15,wihout anemiagroup was higher than ACD group(P=0.042),and two groups were all higher than control group(all P < 0.01).For ACD group,there had significant difference between before and after treatment(P=0.019).1.7 For ERFE,without anemia group were higher than ACD group and control group(P =0.009 and P=0.01),there was no significant difference between ACD with control group(P =0.913).For ACD group,there had significant difference between before and after treatment(P=0.01).1.8 For hepcidin,without anemia group was lower than ACD group(P=0.03),and two groups were all higher than control group(P <0.01).For ACD group,After treatment,hepcidin was lower than befor treatment(P=0.047).2.1 For rh EPO,compared with the control group,the hepcidin mRNA of Hep G2 cells all have significant reduction(P< 0.05),except 5IU/ml group of 12 hours(P=0.617).2.2 Compared with the control group,the hepcidin mRNA of HepG2 cells in the rh TNF-? intervention groups had no significant change(all P> 0.05).2.3 In rhIFN-? group,not only 12 hour groups,but also 24 hour groups all have meaningful increase(all P < 0.01).2.4 For rh IL-6 groups,compare with the control group,the hepcidin m RNA of Hep G2 cells all have significant increase(all P< 0.05).2.5 For rh GDF15 groups,the hepcidin m RNA of Hep G2 cells all have significant reduction(all P< 0.05)?Conclusion?1.EPO combined with intravenous iron supplementation was a safe and effective method for the treatment of ACD in patients with lung cancer.2.The level of serum EPO didnt show a compensatory increase,suggested that EPO was insufficient for ACD.EPO could inhibit the expression of hepcidin m RNA,suggesting that EPO may play an important role in the pathogenesis of ACD in patients with lung cancer.On the one hand,EPO can promote hematopoiesis by overcoming the relative deficiency of EPO,on the other hand,it may indirectly improve anemia by affecting cytokines such as GDF15,hepcidin.3.There was no clear correlation between TNF-?,IL-1 and ACD in patients with lung cancer,and the relationship between IFN-? with ACD in patients with lung cancer needed to be further studied.4.There were significant differences in the levels of IL-6,GDF15,ERFE and hepcidin between the patients of lung cancer with ACD and those without anemia.The levels of GDF15,ERFE and hepcidin with ACD were significantly changed through EPO and intravenous iron treatment,suggested that they play important roles in the pathogenesis of ACD of lung cancer.IL-6 can promote the expression of hepcidin m RNA,conversely GDF15 can inhibit the expression of hepcidin m RNA,indicatethat there are close relationship between IL-6,GDF15 and hepcidin.suggest that they play important roles in the pathogenesis of ACD in lung cancer by affecting hepcidin.