THE ROLE OF MONOCYTE INFLAMMATION AND OXIDANT STRESS IN THE ETIOPATHOGENESIS OF CYSTIC FIBROSIS

1. Z.S. Uyan*, G. Ünlügüzel**, G. Haklar**, E. Çakır*, R. Ersu*, F. Karakoç*, E. Dağlı* *Division of Pediatric Pulmonology, Marmara University, Istanbul, TURKEY **Department of Biochemistry, Marmara University, Istanbul, TURKEY THE ROLE OF MONOCYTE INFLAMMATION AND OXIDANT STRESS IN THE ETIOPATHOGENESIS OF CYSTIC FIBROSIS

2. INTRODUCTION Cystic fibrosis (CF) is the most common recessively inherited lethal disease of Caucasians CF occurs due to mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a transmembrane chloride channel expressed in the epithelium of multiple organs

3. INTRODUCTION Although the organs affected in CF also include the pancreas, gut, liver and reproductive tract, the clinical picture is dominated by pulmonary involvement, with recurrent cycles of infection leading to inflammation and bronchiectasis

4. INTRODUCTION The lung disease of cystic fibrosis is associated with a chronic inflammatory reaction and an overabundance of oxidants relative to antioxidants

5. INTRODUCTION • Chronic bacterial colonisation of lungs leads to infection and inflammation in CF • Increased free radicle formation is seen in CF due to infectious pathology and this increases tendency of CF patients to oxidative damage • In CF, patients have tendency to oxidative stress due to both reduction of antioxidant mechanisms and increased free radicle formation

6. AIM To investigate; the inflammatory status of CF patients the intensity of oxidative stress and free radical damage that CF patients were exposed to compared to non-CF bronchiectasis patients

7. METHOD Children with CF and non-CF bronchiectasis not receiving any steroids for at least two months were enrolled Previous sputum culture results of both CF and non-CF bronchiectasis patients were reviewed

8. METHOD To evaluate oxidative damage intensity, we measured plasma concentrations of malondialdehyde (MDA) To evaluate inflammatory status, we measured hs-CRP levels and oxidative burst of monocytes

9. METHOD Blood samples were taken for hs-CRP MDA monocyte respiratory burst measurement

10. METHOD MDA measurements were done with HPLC and hs-CRP immunoturbidometrically Respiratory burst of monocytes were measured by luminol-enhanced chemiluminescence before and after phorbol-myristate acetate (PMA) induction

11. RESULTS Twenty-six CF cases and eight non-CF bronchiectasis controls were enrolled

12. Table 1.Demographic properties of cystic fibrosis and non-cystic fibrosis bronchiectasis patients Gender (%) (Female / Male) Age (years) Duration of follow-up (years) Cystic Fibrosis 73 / 27 10,9 + 2,9 5,3 + 3,4 Bronchiectasis 37,5 / 62,5 11,6 + 1,8 3,3 + 2,8

13. Figure 1.Etiology of non-cystic fibrosis bronchiectasis patients 12,5% 37,5% 25% 25%

14. Figure2.Previous sputum culture results of cystic fibrosis and non-cystic fibrosis bronchiectasis patients 54% 62,5% 37,5% 46% Patients with non-cystic fibrosis bronchiectasis Patients with cysric fibrosis

15. Figure 3. Microorganisms recovered from previous sputum samples of cystic fibrosis patients 4% 42% 20% 27% 27% of CF patients had more than one microorganism in their sputum cultures

16. Figure 4. Microorganisms recovered from previous sputum samples of non-cystic fibrosis bronchiectasis patients • 37,5% of non-CF bronchiectasis patients had H. influenza in their previous sputum cultures 37;5% 62,5%

17. Figure 5. Mean respiratory function test results of cystic fibrosis and non-cystic fibrosis bronchiectasis patients % of predicted value p>0,5

18. RESULTS Monocyte respiratory burst (PMA induction - basal) activations were significantly increased in CF group compared to the non-CF bronchiectasis cases (5.290.84 vs. 4.60.83 log AUC/mL, p<0.01)

19. Figure 6.Monocyte respiratory burst results of cystic fibrosis and non-cystic fibrosis bronchiectasis patients ΔAUC/ml p<0,01 Cystic fibrosis Bronchiectasis

20. RESULTS Plasma MDA concentrations were also elevated in CF patients compared to non-CF bronchiectasis cases hs-CRP measurements were not different between the two groups

21. CONCLUSION Oxidative stress is more pronounced in CF patients compared to non-CF bronchiectasis cases This could be attributed to systemic nature of the disease

22. CONCLUSION • This is a preliminary study • Patients with CF and non-CF bronchiectasis are still enrolled into the study • Sputum samples of patients are collected to study cytokines in the sputum

23. CONCLUSION There are few studies about antiinflammatory and antioxidant treatment regimens in CF. It is thought that studies like this which are about the etiopathogenesis of CF can guide for studies about treatment of CF.

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