Serum Levels of Seven General Cytokines in Acute Brucellosis Before and After Treatment

Abstract

Purpose Human brucellosis is the most common bacterial zoonosis globally that poses a severe health threat. Despite the availability of antibiotic therapy for human brucellosis, its tendencies of chronicity and persistence may lead to severe debilitating and disabling conditions in patients. Comprehensive understanding of the immune response in brucellosis will be helpful in improving the treatment strategies. In this study, we measured serum levels of T helper cell type 1 (Th1), Th2, and Th17 cytokines in patients with acute brucellosis before and after treatment. Patients and Methods Overall, 30 patients with acute brucellosis from the Beijing Di Tan Hospital and 26 healthy controls were enrolled in this study. All the patients received a 6-week therapy regimen comprising ceftriaxone, doxycycline, and rifampicin. Serum samples were collected from patients with acute Brucella infection and healthy controls before and after treatment. Serum seven cytokine levels of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-6, IL-10), and Th17 (IL-17A) were measured using cytometric bead array. Results In patients with acute infection, the IL-2, IFN-γ, and IL-10 levels were significantly increased compared with those in healthy controls (P < 0.001). After treatment, IL-2, IFN-γ, and IL-10 levels significantly decreased (P < 0.05) and the TNF-α level significantly increased compared with the corresponding baseline levels and those in healthy controls (P < 0.05). Furthermore, the IFN-γ, IL-4, and IL-10 levels were higher in patients after treatment than in healthy controls (P < 0.05). IL-2 and IL-6 levels exhibited a positive correlation with the C-reactive protein (CRP) level in acute brucellosis (P < 0.05). Conclusion Levels of most serum Th1 and Th2 cytokines were simultaneously increased in acute infection, followed by reduction in the corresponding cytokine levels and residual cytokine response during treatment. This residual immune response could represent a therapeutic opportunity that may improve the long-term clinical outcomes in patients with acute brucellosis after treatment.

Intracellular Growth Inhibition and Host Immune Modulation of 3-Amino-1,2,4-triazole in Murine Brucellosis

“…Our study revealed that the serum concentrations of TNF-α and IL-6 or IFN-γ and IL-10 in B. abortus-infected mice receiving 3-AT were notably reduced compared to those of the infected group without 3-AT treatment, yet they were still higher than the levels observed in the non-infected group. These results are consistent with the cytokine profiles observed in human brucellosis [41][42][43].…”

“…The cytokine levels and the CD4 + /CD8 + ratio pattern can serve as indicators of the immune status in brucellosis. In the acute phase of brucellosis, infected patients exhibit higher levels of cytokines, such as TNF-α, IL-6 or IFN-γ, and IL-10, compared to Brucella-negative individuals [41][42][43][44]. In the convalescent stage, these cytokines are reduced compared to pre-treated patients but remain elevated compared to healthy cases [43].…”

“…In the acute phase of brucellosis, infected patients exhibit higher levels of cytokines, such as TNF-α, IL-6 or IFN-γ, and IL-10, compared to Brucella-negative individuals [41][42][43][44]. In the convalescent stage, these cytokines are reduced compared to pre-treated patients but remain elevated compared to healthy cases [43]. Our study revealed that the serum concentrations of TNF-α and IL-6 or IFN-γ and IL-10 in B. abortus-infected mice receiving 3-AT were notably reduced compared to those of the infected group without 3-AT treatment, yet they were still higher than the levels observed in the non-infected group.…”

Effectiveness of Brucellosis on Polymorphisms of IL-1B and IL-10 Concentrations Among Iraqi Patients

“…Also the mean of anti Brucella IgG antibodies concentration in Brucellosis patients was significantly higher than the control group, which was matched with (Guzmán-Bracho, et al, 2020) who reported that in the stage of chronic infection with Brucella, the immune system is occupied with the production of antibodies and defense cells, especially since there is no effective treatment that kills this bacteria that is transmitted through animals by drinking unsterilized milk, there will be a high rise and strong reaction of the immune system constantly [17]. The mean of IL-10 concentration in Brucellosis patients was significantly higher compared to the control group, a result that was matched with (Tang, et al, 2021) who confirmed that in acute brucellosis, the levels of IL-2, IL-10 & IFN-γ are significantly elevated in comparison with the healthy individuals [18]. Also, the mean of IL-1B concentration in Brucellosis patients was significantly higher than the control group.…”

Immunosuppressive Mechanisms in Brucellosis in Light of Chronic Bacterial Diseases

“…Moreover, genetic associative studies identified single nucleotide polymorphisms linked to brucellosis susceptibility in the TGFB gene [ 153 , 154 ]. IL-10, another cytokine well-known for its ability to inhibit the development of Th1 type responses [ 155 ], is also induced during B. abortus infection in the mouse model [ 140 , 156 , 157 ] and increased in serum from acute and chronic patients [ 158 , 159 ]. IL-10 −/− mice produce higher levels of IFN-γ and better eliminate B. abortus than WT animals [ 160 ]; in addition, by modulating macrophage functions, IL-10 contributes to create an environment that allows enhanced bacterial survival and persistent infection [ 161 ].…”