concanavalin-a and Erythema-Nodosum

The complex symptoms observed in lepromatous leprosy patients with reactive episodes of the erythema nodosum leprosum (ENL) type are associated with different serum components actively participating in the acute inflammatory reaction. Among them are the tumor necrosis factor (TNF) and the acute-phase protein C-reactive protein (CRP). TNF and CRP were found at significantly more elevated concentrations in the serum of patients with ENL, with a positive correlation of about 95% when compared with patients with nonreactive lepromatous leprosy (L) or tuberculoid leprosy (T) or with control individuals. Furthermore, in another series of experiments CRP had a specific and significant suppressive action on concanavalin A (ConA)-induced lymphoproliferation in cultures from patients and controls, the reduction being more marked (75%) in patients with ENL. By extrapolation from its known actions, production of TNF may have a number of potential consequences for the immunobiology of ENL. Thus, TNF may cause direct injury to compromised cells, facilitating mononuclear cell activation and production of cytokines such as interleukin-1 and interleukin-6, and upregulating hepatocyte expression of CRP. Both CRP and TNF in high serum concentrations have the ability to enhance the acute inflammatory process in ENL, favoring increased macrophage activation and phagoctyosis, and contributing to the elimination of damaged cells and bacilli, as well as in the reduction of T-suppressor cells, with a consequent improvement in the immunologic response of ENL patients.

Topics: Adolescent; Adult; C-Reactive Protein; Concanavalin A; Erythema Nodosum; Female; Humans; Immunosuppression Therapy; Leprosy, Lepromatous; Leprosy, Tuberculoid; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes; Tumor Necrosis Factor-alpha

The contribution of non-specific suppressor mechanisms to the overall immunoregulatory defect observed in lepromatous leprosy was evaluated. Con A-induced suppression was assayed using the standard two-stage test in 27 lepromatous leprosy patients, 19 of them during the quiescent stage (LL) and eight during erythema nodosum lepromatosum (ENL). Lymphocytes from normal individuals react in this assay, yielding higher suppression as the numbers of Con A-induced suppressor cells (Leu 2a+ cells) increase. In contrast, two patterns of response were observed in both LL and ENL patients: those giving lower suppression as the number of suppressor cells increased (LL-A and ENL-A) and those responding with the normal pattern (LL-B and ENL-B). The abnormal dose-response profile was not related to the disease stage, as both ENL and LL patients were included in groups with normal or atypical response. Reaction of the potential suppressor cells with anti-Leu 2a antibody abolished suppression in LL-B and normals, whereas Con A-induced suppression was unchanged or higher in ENL-A, ENL-B and LL-A, indicating that in these patients Leu 2a+ cells interfered with the generation of Con A-induced suppression. The contribution of spontaneous suppression was examined and it was shown that suppressor activity in the absence of Con A stimulus was higher in ENL (both ENL-A and ENL-B) and LL-A. Thus, it appears that the occurrence of high spontaneous suppressor activity, probably related to in vivo activation, is associated with a relative inability to generate de novo suppression after Con A stimulation in these patients.

Topics: Adult; Aged; Antibodies, Monoclonal; Concanavalin A; Erythema Nodosum; Female; Humans; Immune Tolerance; Leprosy; Male; Middle Aged; T-Lymphocytes, Regulatory

ConA-induced suppressor activity in patients with lepromatous leprosy (LL) was studied. Patients were studied during and after erythema nodosum leprosum (ENL) reactions. The study included 16 patients with ENL, nine of whom returned once the ENL episode was over. Patients were compared to 12 normal controls. Suppressor activity was evaluated in vitro by cultivating peripheral blood lymphocytes (PBL) with an inducer of T suppressor cells, concanavalin A (ConA), and with two different mitogens, phytohemagglutinin (PHA) and ConA, in order to measure the inhibition of the proliferative responses in all cases. In contrast, in LL patients during ENL the ConA-induced suppressor response was markedly reduced. The reduction in suppressor responses was even more marked in the LL patients after the ENL episode. Reduced levels of suppressor activity in LL patients reveal a defect in central mechanisms of control in the immune response.

Topics: Adult; Concanavalin A; Erythema Nodosum; Female; Humans; Leprosy; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes, Regulatory

Peripheral blood lymphocytes from nine normal subjects and 40 patients with leprosy were pretreated in vitro with Concanavalin A (Con A). Cells from normal subjects pretreated for 24 hours showed consistent and effective generation of suppressive activity which inhibited mitogen induced transformation of autologous lymphocytes. Prolongation of Con A pretreatment to 40 hours resulted in maximal suppressive activity. Tuberculoid leprosy patients had lymphocytes in their blood which on 24 hour pretreatment with Con A exerted suppressive effects markedly greater than the maximal suppression noted with 40 hour pretreated normal lymphocytes. In contrast, untreated patients with polar lepromatous leprosy showed a decrease in suppressive activity which could not be altered by prolongation of Con A pretreatment: the loss of suppressive activity noted in this form of leprosy was restored during erythema nodosum leprosum.

Topics: Concanavalin A; Erythema Nodosum; Humans; Leprosy; Lymphocyte Activation; Mitogens; Mitomycins; Mycobacterium Infections, Nontuberculous; Mycobacterium leprae; T-Lymphocytes, Regulatory