| Sažetak | Ovaj rad obuhvaća rezultate uloge beta kemokina i metaloproteinaza u imunopatogenezi pneumonije koju uzrokuje mikoplazma pneumonije. Svi bolesnici uključeni u istraživanje liječeni su u Klinici za infektivne bolesti (KIB) «Dr. Fran Mihaljević» u Zagrebu. U ispitivanje je ukupno uključeno 40 bolesnika muškog spola s atipičnom pneumonijom koju je uzrokovala mikoplazma pneumonije. Klinička dijagnoza pneumonije iz opće populacije definirana je akutnim početkom s povišenom temperaturom i rendgenskom potvrdom plućnog infiltrata. Etiološka dijagnoza bolesti potvrđena je serološkim testiranjem. Kontrolna skupina obuhvaća 20 zdravih muških ispitanika slične dobi kao bolesnici. Prosječna životna dob naših bolesnika bila je 19 godina. Bolesnici su hospitalizirani najčešće petog dana bolesti. Klinička slika u naših bolesnika je bila blaga do srednje teška, što odgovara laboratorijskim nalazima kod prijema. Rendgenska snimka pluća registrira intersticijske upalne infiltrate u jednom (28 ili 70%), odnosno više režnjeva (12 ili 30%), a pleuralni izljev se bilježi u 6 ili 15% bolesnika. Na primjenjenu antibiotsku terapiju u svih bolesnika polučio se vrlo dobar klinički učinak. Tijekom hospitalizacije nisu zabilježene ozbiljnije komplikacije bolesti. Niti u jednom od ispitivanih uzoraka bolesnika, kao niti kontrolne skupine nije se registrirala ekspresija gena za MMP-2. U 31 bolesnika u akutbnom stadiju bolesti, 30 rekonvalescenata, odnosno 19 kontrolnih ispitanika bilježi se ekspresija gena za IL-8, MCP-1, MIP-1β i MMP-9. Ekspresija gena za MCP-1 bila je smanjena u većine bolesnika i nije se bitno razlikovala između naših bolesnika i kontrolne skupine. Ekspresija gena za IL-8 bila je statistički značajno povišena u bolesnika u akutnoj fazi bolesti i rekonvalescenciji u odnosu na kontrolnu skupinu (Mann-Whitney test; p=0,013; p=0,001). Isto tako, espresija gena za MIP-1β bila je statistički značajno povišena u bolesnika u akutnoj fazi bolesti i rekonvalescenciji u odnosu na kontrolnu skupinu (Mann-Whitney test; p<0,001; p=0,001). Ekspresija gena za MMP-9 bila je statistički značajno povišena u akutnoj fazi bolesti u odnosu na kontrolnu skupinu i rekonvalescente (Mann-Whitney; p=0,001; p=0,016). Spearmanovim testom korelacije u naših bolesnika nađe se značajna korelacija između genske ekspresije MIP-1β i broja neutrofila u perifernoj cirkulaciji. Koncentracija IL-8, MCP-1, MIP-1β, MMP-2 i MMP-9 u serumu učinjena je u 39 bolesnika u akutnoj fazi bolesti, 36 rekonvalescenata i 12 kontrolnih ispitanika. Analizirajući razinu ispitivanih kemokina i metaloproteinaza registrira se statistički viša razina IL-8 u bolesnika u akutnoj fazi u odnosu na kontrolnu skupinu (Mann-Whitney test; p=0,033). Isto tako, razina MMP-9 bila je viša u odnosu na kontrolne ispitanike, no bez statističke značajnosti (Mann-Whitney test; p=0,062). Vrijednosti MCP-1 i MMP-2 su u akutnih bolesnika bile statističke značajno niže nego u kontrolnoj skupini (Mann-Whitney test; p=0,012; p=0,001) dok se razina MIP-1β nije bitno razlikovala između bolesnika i zdravih ispitanika. Spearmanovim testom korelacije nađe se statistička značajna korelacija između broja leukocita u perifernoj cirkulaciji i serumske razine IL-8 u naših bolesnika. Nije se našla statistički značajna razlika u koncentraciji IL-8 i MMP-9 u bolesnika koji su imali pleuralni izljev (Mann-Whitney test; p=0,613; p=0,726). Također nije nađena statistički značajna razlika u koncentraciji IL-8 i MMP-9 između bolesnika koji su imali zahvaćena dva ili više plućnih režnjeva (Mann-Whitney test; p=0,228; p=0,403). Ovi rezultati mogli bi pridonijeti daljnjim istraživanjima koja bi trebala objasniti imunopatogenetske mehanizme koji stoje u pozadini pneumonije uzrokovane mikoplazmom pneumonije. |
| Sažetak (engleski) | The results of research on the role of beta-chemokines and metalloproteinases in the immunopathogenesis of pneumonia caused by mycoplasma pneumoniae are presented in the dissertation. All patients included in the research were treated at the University Hospital for Infectious Diseases "Dr Fran Mihaljevic" in Zagreb. A total of 40 male patients with atypical pneumonia caused by mycoplasma pneumoniae were included in this research. Clinical diagnosis of community acquired pneumonia was defined as acute infection with increased temperature and roentgenological finding of pulmonary infiltrate. Etiological diagnosis of disease was confirmed with serological testing. A control group included 20 healthy male examinees of similar age as the patients. The average age of our patients was 19 years. The patients were most commonly hospitalized on the fifth day of illness. Clinical presentation of disease was mild up to moderately severe, in accordance with laboratory results on admission. Chest X-ray recorded interstitial inflammatory infiltrates in one (28 or 70%), or multiple lobes (12 or 30%), and pleural effusion was recorded in 6 or 15% of patients. Favorable clinical response to administered antibiotic therapy was recorded in all patients. More severe disease complications were not recorded during hospitalization. MMP-2 gene expression was not recorded in any sample obtained from patients, nor from the control group of examinees. In 31 patients with acute stage of disease, 30 reconvalescents, i.e. 19 control examinees we recorded gene expression of IL-8, MCP-1, MIP-1β and MMP-9. MCP-1 gene expression was decreased in the majority of patients and did not significantly differ between the patients and the control group. IL-8 gene expression statistically significantly increased in patients in the acute phase of disease and during reconvalescence compared to the control group (Mann-Whitney test; p=0,013; p=0,001). Similarly, gene expression of MIP-1β was statistically significantly increased in patients in the acute phase of disease and in reconvalescence compared to control group (Mann-Whitney test; p<0,001; p=0,001). MMP-9 gene expression was statistically significantly increased in the acute phase of illness compared to control group and reconvalescents (Mann-Whitney; p=0,001; p=0,016). Spearman`s correlation test in our patients showed correlation between gene expression of MIP-1β and neutrophils count in peripheral circulation. The concentration of IL-8, MCP-1, MIP-1β, MMP-2 and MMP-9 was measured in the serum of 30 patients in the acute phase of disease, 36 reconvalescents and 12 control examinees. By analyzing the level of examined chemokines and metalloproteinases, we recorded a statistically higher level of IL-8 in patients in the acute phase of illness than among those in the control group (Mann-Whitney test; p=0,033). Similarly, the level of MMP-9 was higher compared to control examinees, but without statistical significance (Mann-Whitney test; p=0,062). The levels of MCP-1 and MMP-2 in acute patients were statistically significantly lower than in the control group of patients (Mann-Whitney test; p=0,012; p=0,001) while the level of MIP-1β did not significantly differed between the patients and healthy examinees. Spearman`s correlation test showed statistical significance correlation between leukocytes count in peripheral circulation and IL-8 levels in the patients`s sera. No statistically significant difference was found in IL-8 and MMP-9 concentration in patients with pleural effusion (Mann-Whitney test; p=0,613; p=0,726). Also, no statistically significant difference was detected in IL-8 and MMP-9 concentration between patients with two or more pulmonary lobes affected (Mann-Whitney test; p=0,228; p=0,403). These results could contribute to further research that should explain immunopathogenic mechanisms in pneumonia caused by mycoplasma pneumoniae. |
