Cytokines in human immunodeficiency virus type 1 inefction

Cilj ovog istraživanja bio je usporediti ekspresiju citokina na razini gena i proteina u akutnoj i kroničnoj fazi infekcije HIV-om-1, te analizirati učinak dugotrajne supresije virusne replikacije u periodu duljem od dvije godine na citokinsku imunost. U dio istraživanja koji se bavi usporedbom citokinske imunosti na proteinskoj razini u akutnoj i kroničnoj fazi infekcije uključila sam 34 ispitanika, dok sam u istraživanje učinka dugotrajne supresije virusne replikacije na ekspresiju citokina u infekciji HIV-om-1 uključila 80 ispitanika. Ekspresiju 84 citokinska gena analizirala sam u tri ispitanika u akutnoj i tri u kroničnoj infekciji HIV-om-1 metodom „PCR array“. Za kvantifikaciju Th1/Th2/Th9/Th17/Th22 citokina primjenila sam citometriju pomoću kuglica (bead-based cytometry). U kroničnoj infekciji HIV-om-1 dokazala sam statistički značajno povećanje ekspresije 13 citokinskih gena (cd40lg, csf2, ifna5, il12b, il1b, il20, lta, osm, spp1, tgfa, tnfsf 11,14 i 8), te sniženje ekspresije il12a. U akutnoj fazi je u odnosu na kontrolnu skupinu došlo do povećanja koncentracija IL-10, IL-4 i TNF-α. Povećane koncentracije IL-10 i TNF-α, te uz njih IL-2, IL-6, IL-13 i IL-22 otkrivene su u kroničnoj infekciji u odnosu na kontrolu. Usporedbom ekspresije citokina između dviju faza infekcije HIV-om-1 vidljivo je smanjenje koncentracija IL-9. Koncentracija IL-17A snižena je u ispitanika prije primjene antiretrovirusne terapije, a kod kojih je dokazana supresija virusne replikacije. Ekspresija aktivacijskih biljega CD38 i HLA-DR snižena je u kroničnoj u odnosu na akutnu infekciju, te u supresiji virusne replikacije u odnosu na uzorke prije primjene terapije. U ovom je istraživanju dokazana promjena citokinskih profila u infekciji HIV-om-1 između akutne i kronične faze na razini genske i proteinske ekspresije.The aim of this study was to compare cytokine expression on both gene and protein levels in acute and chronic phase of HIV type 1 infection and to analyze the effect of long-term suppression of viral replication in period longer than 2 years on cytokine immunity. To analyze cytokine expression on protein level in acute and chronic phase of HIV type 1 infection 34 patients were enrolled and the effect of long-term suppression of viral replication was determined in 80 HIV-positive patients. Using PCR array technology, expression of 84 cytokine genes was measured in 3 patients in acute and 3 patients in chronic phase of HIV type 1 infection. Bead-based cytometry was used to quantify levels of Th1/Th2/Th9/Th17/Th22 cytokines. The results showed statistically significant increase of 13 cytokine gene expression (cd40lg, csf2, ifna5, il12b, il1b, il20, lta, osm, spp1, tgfa, tnfsf 11, 14 and 8) and down regulation of the il12a expression in chronic HIV type 1 infection. Concentrations of IL-10, IL-4 and TNF-α were increased in the acute HIV type 1 infection when compared to control group. During chronic HIV type 1 infection there was an increase of IL-10, TNF-α, IL-2, IL-6, IL-13 and IL-22 levels when compared to control group. Comparison of cytokine expression between two stages of infection showed significant decrease in IL-9 concentration. Level of IL-17 was lower in therapy-naive patients with a suppression of viral replication. Expression of activation markers CD38 and HLA-DR was lower in a chronic stage of infection compared to acute infection as well as in samples with suppression of viral replication compared to samples before therapy initiation. This study showed change in cytokine profile in both gene and protein expression in different stages of HIV-infection