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Objectives and Methods: Despite the treatment, a considerable proportion of brucellosis patients develop chronic disease, characterized by atypical clinical picture and/or relapses. Th1 cytokines are critical for the clearance of Brucella infection and diminished production of IL-2 in response to PHA, has been described in chronic brucellosis. In order to investigate the role of IL-2R alpha (CD25) in disease outcome, we evaluated the ex vivo and PHA-induced percentage of peripheral CD4+ T-lymphocytes expressing CD25 in 13 acute brucellosis patients (AB), 22 chronic brucellosis patients (CB), 11 "clinically cured" subjects and 15 healthy volunteers (controls). Simultaneously, CD3+, CD4+ and CD8+ T-lymphocytes subsets were measured., Results: The ex vivo percentage of CD4+/CD25+ T-cells was significantly higher in AB patients compared to "clinically cured" subjects (p=0.005) and controls (p=0.006). By contrast, CD4+/CD25+ T-cells were significantly lower in CB patients (p=0.001). T-lymphocytes subsets did not significantly differ between the groups. After PHA stimulation, CD4+/CD25+ T-cells remained significantly lower in CB and specifically in the relapsing form of chronic disease compared to AB (p=0.044, 0.023). Additionally, CD8+ T-lymphocytes were found to be significantly increased in CB and mainly in the relapsing subgroup of CB patients compared to AB (p=0.044, 0.011)., Conclusion: Diminished percentage of peripheral CD4+ T-lymphocytes expressing IL-2R alpha is associated with chronic relapsing brucellosis.

Despite treatment, 10-30% of brucellosis patients develop chronic disease, characterized by atypical clinical picture and/or relapses. A defective T helper 1 (Th1) response and a low [corrected] percentage of CD4(+)/CD25(+) cells have been described in chronic brucellosis patients. CD80/CD28 co-stimulation is critical for an efficient Th1 response and has not been studied previously in human brucellosis. In order to investigate the role of CD80/CD28 co-stimulation, 13 acute brucellosis patients (AB), 22 chronic brucellosis patients (CB, 12/22 relapsing type-CB1 and 10/22 atypical type-CB2), 11 'cured' subjects and 15 healthy volunteers (controls) were studied. The percentage of CD4(+)/CD28(+) T lymphocytes and CD14(+)/CD80(+) monocytes were analysed by flow cytometry both ex vivo and after phytohaemagglutinin (PHA)-stimulation with or without heat-killed Brucella abortus (HkBA). Ex vivo analysis showed no differences between all groups studied. PHA stimulation up-regulated the percentage of CD80(+) monocytes in AB compared to 'cured' subjects and controls (P < 0.001), although the proportion of CD4(+)/CD28(+) cells did not alter. A higher percentage of CD80(+) monocytes was observed in the CB1 subgroup, compared to AB, 'cured' subjects and controls (P = 0.042, < 0.001 and < 0.001, respectively). CB2 was characterized by a lower percentage of CD80(+) monocytes in comparison to CB1 (P = 0.020). HkBA in PHA cultures down-regulated the percentage of CD80(+) monocytes compared to PHA alone in all groups, especially in AB and CB patients (P < 0.001 and P = 0.007, respectively). In conclusion, the diminished percentage of CD4(+)/CD25(+) T cells in CB is not associated with inadequate CD80/CD28 co-stimulation. We speculate that differential frequency of CD80(+) monocytes after PHA stimulation could serve as a qualitative parameter of disease status, related to the different clinical forms of chronic brucellosis.

Brucellosis is a zoonosis of worldwide distribution presenting with a wide clinical spectrum. Brucellosis can involve any organ or system. The axial skeleton is the most common site of involvement with a frequency ranging from 2% to 53%. Multiple-level spinal involvements are rare. This report describes the first case of noncontiguous synchronous multifocal involvement of all cervical, thoracic, and lumbar regions in a patient with brucellar spondylodiscitis.

Thirty two anergic patients with chronic brucellosis treated with a) interferon-alpha 2b(group 1), b) levamisole (group 2) and c) conventional therapy(group 3) were studied. The effect of treatment on T lymphocyte blast formation in the presence of PHA, specific cell mediated immunity against brucella antigens, titers of brucella antibodies and clinical symptoms were evaluated .T lymphocyte blast formation was shown to range in normal levels in all patients before treatment compared to 10 normal controls suggesting against a generalized impairment of cell mediated immunity. Titers of brucella antibodies were significantly decreased in group 1, almost significantly in group 2 and were significantly increased in group 3 at the end of treatment. A significant improvement of symptoms as well as production of leukocyte migration inhibition against brucella antigens were noted in both groups 1 and 2, in contrast to group 3. This response to treatment was however greater in group 1. These findings demonstrate that immunotherapy resulted in both clinical and immunological improvement and that interferon seems to be a more promising therapeutic approach of chronic brucellosis.

The in vitro effect of IFN-a on lymphocyte transformation and specific immune response against Brucella antigens was studied in 33 patients with chronic brucellosis and 10 normal controls. The following immunologic in vitro tests were applied: PHA activated lymphocyte transformation test using Bromodeoxyuridine and a monoclonal antibody in the presence and absence of 50 and 100 IU IFN Alpha-2b and leukocyte migration inhibition test against Brucella antigens in the presence and absence of 100 and 500 IU of IFN Alpha-2b. Patients were further divided to 2 subgroups according to a positive or negative migration inhibition test. Our results showed that T lymphocyte transformation was similar in patients and controls and that the addition of 50 IU IFN resulted in a significant increase of transforming cells whereas in the concentration of 100 IU IFN only anergic patients and controls responded positively. IFN also resulted in a significant leukocyte migration inhibition only in anergic patients and controls. These findings suggest that the chronic infection is not due to a generalized cellular immunodeficiency state and that IFN Alpha-2b might be a promising therapeutic approach in anergic patients.

Ten patients with chronic brucellosis were treated with levamisole, 150mg daily for 3 consecutive days every week for 6 months. Patients were followed up for another 6 months after the end of treatment. By the end of the treatment period, patients improved clinically, their E rosettes showed a significant increase and specific leukocyte inhibition migration factor (LIF) was produced. By the end of the follow up period, all patients except one became symptom free, antiglobulin titers were very low or negative, E rosettes showed a further increase ranging to normal levels and specific LIF activity was not detected to most of the patients. Our results suggest that levamisole might prove to be beneficial in the treatment of chronic brucellosis.

Peripheral blood monocyte phagocytosis of SRBC was studied in 32 patients with chronic brucellosis and 20 normal controls. It was found that phagocytosis was significantly decreased in patients with chronic brucellosis. Our findings suggest that disfunction of this cell-system in chronic brucellosis could be responsible for the chronicity of the disease.

The in vitro effect of levamisole on peripheral blood monocyte (P.B.M.) phagocytosis was studied in 32 patients with chronic brucellosis and 20 normal subjects. It was shown that levamisole enhances P.B.M. phagocytic capacity, not reaching however normal levels. A subgroup of 11 patients were treated with levamisole for 6 months and the drug effect on cellular and humoral immunity and monocyte phagocytosis was also studied. By the end of the 6 month treatment-study period, the following results were obtained: 1. six patients were symptom free while five had significantly improved. 2. T lymphocyte number and monocyte phagocytosis reached normal values. 3. Significant specific cellular immunity against both brucella antigens was noted. 4. B. lymphocytes showed no significant changes. 5. Antiglobulin titers varied. These findings suggest that the good therapeutical effect of levamisole in patients with chronic brucellosis could probably be a attributed to the enhancement of both T-cell function and monocyte phagocytosis.