Cytokines in leprosy, I. Serum cytokine profile in leprosy.

BACKGROUND: Leprosy is a chronic infectious disease characterized by a broad spectrum of clinical forms depending on the patient's immune response, in particular cell-mediated immune response. METHODS: Cytokines can play a role in the cell-mediated immune response. Serum levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-2 receptor (IL-2R), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) were measured by enzyme-linked immunosorbent assay (ELISA) in 55 untreated leprosy patients and 35 reactional leprosy patients, in addition to 20 age- and sex-matched healthy controls. RESULTS: Leprosy patients showed significantly higher serum levels of the studied cytokines (except IL-2) compared with healthy controls. When the two poles were compared, tuberculoid leprosy (TT) patients showed significantly higher levels of IFN-gamma and TNF-alpha with significant negative correlations with the bacterial index (BI), whereas lepromatous leprosy (LL) patients showed significantly higher serum levels of IL-2R, IL-10, and IL-1beta with significant positive correlations with the BI. Both type I and type II reactional patients showed significantly higher serum IFN-gamma, IL-2R, and IL-1beta, in addition to IL-10 in type II reactional patients, compared with nonreactional leprosy patients. When compared with each other, type I reactional patients showed increased levels of IFN-gamma, whereas type II reactional patients showed increased levels of IL-10. CONCLUSIONS: In leprosy patients, both IFN-gamma and TNF-alpha are immunoprotective, whereas IL-2R, IL-10, and IL-1beta are immunosuppressive. Our results indicate that type I reaction, with increased levels of IFN-gamma, is a cell-mediated immune response, whereas type II reaction, with increased levels of IL-10, is essentially an immune complex disease.

Cytokines in leprosy, II. Effect of treatment on serum cytokines in leprosy.

BACKGROUND: Multidrug therapy (MDT) causes a decrease in the bacterial burden in leprosy patients. Does the decrease in the antigenic stimulation of the immune system have an effect on cytokine production? METHODS: The effect of treatment on serum cytokines was evaluated in 36 leprosy patients and 35 reactional leprosy patients and compared with that in 20 age- and sex-matched healthy individuals. The enzyme-linked immunosorbent assay (ELISA) technique was used to measure serum levels of interleukin-2 receptor (IL-2R), interleukin-10 (IL-10), and interleukin-1beta (IL-1beta) before and after treatment. These cytokines represent T-helper 1 (TH1), T-helper 2 (TH2), and macrophage cytokines, respectively. RESULTS: The studied serum cytokines were significantly reduced after 1 year of treatment in leprosy patients. The degrees of reduction were significantly positively correlated with a reduction in the bacterial index (BI) and morphologic index (MI). After 1 year of MDT (but not 6 months), paucibacillary (PB) patients showed a significant reduction in all the studied serum cytokines to levels comparable with those of healthy controls. Multibacillary (MB) patients also showed a significant reduction in all the studied serum cytokines, but the levels were still significantly higher than those of healthy controls. Leprosy patients with high levels of serum IL-1beta were more susceptible to the development of reactions after the initiation of treatment. Corticosteroid therapy of reactional patients resulted in a significant reduction in the studied serum cytokines to levels similar or lower than those of nonreactional leprosy patients. The dose of steroids showed a significant positive correlation with the amount of decrease in IL-1beta. CONCLUSIONS: MDT caused a reduction in serum cytokines correlated with a reduction in the bacterial burden. It is advisable to continue MDT for PB patients for 1 year. Serum IL-1beta levels may have a prognostic value for the susceptibility of leprosy patients to the development of reactions.