Mystery of immune response in relapsed brucellosis immunophenotyping and multiple cytokine analysis

Abstract

Introduction: Brucella spp. are intracellular bacteria that may cause acute, subacute and chronic infections. Although optimum antibiotic treatment is available, relapse of brucellosis occurs in some patients. There isless amount of knowledge about immune response in relapse of brucellosis. Materials and Methods: Twenty patients with acute brucellosis and sixteen patients with relapse brucellosis were enrolled in this study to explore the immune response variation during relapse of brucellosis. The distribution of peripheral blood mononuclear cells investigated by flow cytometry and various cytokines levels involved in inflammatory and anti-inflammatory response, measured by ELISA in serum samples. Results: The most prominent data in phenotyping examination was the significant 1.45 times reduction at the percentage of activated T cell (CD3+HLA-DR+ ) population in the relapse group in comparison to acute brucellosis. However, percentage of activated T cell population in the relapse group was 2.59 times higher than the healthy group (p<0.01). In case of cytokine levels; we observed significant reduction at inflammatory cytokines IL-6, IL-18, IFN-g and IL-17 in relapsed patients in comparison to patients with acute brucellosis. While there was no significant difference in IL-15 and TNF-a levels between relapse and acute brucellosis group; the levels of these two cytokines were significantly higher in the relapse group than healthy subjects. Interestingly, we observed 2.87 times elevation ofIL-4 levels in the relapse group in comparison to acute brucellosis (p<0.01). Similarly; IL-10 levels increased 2.09 times in patients with relapsed brucellosis patients in comparison to acute brucellosis (p<0.01). Conclusion: Elevation of regulatory cytokinesin systemic immune system, and reduction of activated T cell frequency occur during the relapse of brucellosis. These results may have important consequences to understand the immunopathology in the systemic circulation during relapse of brucellosis.