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. Despite optimum antibiotic treatment, relapse of brucellosis occurs in some patients. There is less amount of knowledge about immune response in relapse of brucellosis. Materials and Methods: Twenty patients with acute brucellosis, 16 patients with relapsed brucellosis and as a control group 20 healthy volunteers were enrolled in this study to explore the immune response variation during relapse of brucellosis. The distribution of peripheral blood mononuclear cells was investigated by flow cytometry and level of various cytokines involved in inflammatory and anti-inflammatory response were measured by enzyme-linked immunosorbent assay in serum samples. Results: The most prominent data in phenotyping examination was the significant reduction (1.45 times) in the percentage of activated T cell (CD3+human leukocyte antigen-DR+) population in the relapse group in comparison to the acute brucellosis group. However, percentage of activated T cell population in the relapse group was 2.59 times higher than in healthy controls (p<0.01). We observed a significant reduction in inflammatory cytokines interleukin (IL)-6, IL-18, interferon-g and IL-17 in relapsed patients in comparison to patients with acute brucellosis. While there was no significant difference in IL-15 and tumor necrosis factor-a levels between relapse and acute brucellosis groups, the levels of these two cytokines were significantly higher in the relapse group than in healthy subjects. In case of anti-inflammatory cytokines, while IL-4 levels increased significantly only in relapse group, IL-10 levels increased both in acute and relapse brucellosis group in comparison to healthy controls. Interestingly, we observed 2.87 times elevation in IL-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 cytokines in systemic immune system and reduction of activated T cell frequency occur during the relapse of brucellosis. These results may contribute to understanding the immunopathology in the systemic circulation during relapse of brucellosis.

Keywords

• Brucellosis
• cytokines
• immune response
• relapse
• tumor necrosis factor alpha