Dapsone, clofazimine and rifampicin, the three most important constituents of multidrug therapy against leprosy, were studied with respect to their effects on the rat serum complement system, in vitro as well as in vivo. Of the three drugs only dapsone and clofazimine exhibited significant in vitro anti-complement activity and only at a very high, non-therapeutic dose of 0.24 mg/ml. On the contrary, rifampicin could not induce significant in vitro complement consumption. Furthermore, dapsone and clofazimine could reduce rat-serum-mediated rabbit erythrocyte haemolysis in the presence of Mg2+-EGTA, indicating that they could also affect the alternative pathway of complement activation. However, the latter pathway of complement consumption by these drugs seems to be insignificant because the factor-B-mediated complement-consumption system is minimal in rat sera. Immunoelectrophoretic study of mixtures of fresh rat sera and anti-leprosy drugs against specific anti-rat-C3 antisera demonstrated that dapsone and clofazimine could not cleave the C3 complement component. In a separate experiment we attempted to reconstitute the haemolytic complement activity consumed by dapsone and clofazimine by adding Crat-EDTA sera (a source of C3, C5, C6, C7, C8 and C9), but at most only 12% reconstitution of haemolytic activity could be achieved. We thus conclude that both dapsone and clofazimine could affect the complement system, predominantly through the earlier complement components and at very high, non-therapeutic doses. On the contrary, in-vivo experiments in rats showed that a combination of these three drugs, when given at a therapeutic dose or at 10 times the therapeutic dose for three months, did not affect the complement system.

Animals↗

PubMedDate not supplied

Blood, bone marrow and splenic lymphocyte subset profiles in Indian visceral leishmaniasis.

We examined the lymphocyte subsets in peripheral blood, bone marrow and spleen of 11 patients with acute visceral leishmaniasis (VL) and 9 with chronic VL before and after 8 weeks of antileishmanial therapy. On admission, the CD4 cell count was depressed in the peripheral blood of acute and chronic VL cases as compared to the value in 10 normal control subjects. In contrast, CD4 cell counts were higher in the bone marrow in acute and chronic cases, and in splenic aspirates of chronic cases only, compared to normal values. The peripheral blood CD8 cell count, while normal in acute cases, was uniformly low in chronic cases. Counts of CD8 cells were also low in bone marrow of acute and chronic cases, as well as in splenic aspirates of chronic cases only. All these differences were significant (P < 0.05). After treatment, the CD4 cell count in the peripheral blood increased, but decreased in bone marrow and splenic aspirates. The CD8 cell count remained unaltered in the peripheral blood but increased significantly (P < 0.05) in bone marrow and spleen. The results suggest that in VL the peripheral blood picture may not reveal the actual T cell subset profile in the reticuloendothelial system. The changes in CD8 cell counts in the bone marrow and spleen seem to be independent, and are probably influenced by antileishmanial therapy.

Acute Disease↗

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Reversion of the downhill course of active lepromatous leprosy by repeated transfusions of fresh blood, donated by healthy but lepromin positive patients.

Earlier studies of immunologic reconstitution therapy of active lepromatous leprosy patients by repeated infusions of viable allogeneic blood lymphocytes indicated a beneficial effect. In order to avoid cell separation and its associated risks, we attempted to transfer immunity passively into seven seriously ill lepromatous patients by repeated transfusions of fresh blood donated by healthy, but tuberculin and lepromin positive, subjects. The results showed clinical improvement in some cases with the elimination of Mycobacterium leprae, histological reversion and return of immunologic responsiveness.

Adult↗

PubMedDate not supplied

Reversal reaction in patients with lepromatous leprosy after transplantation of human fetal thymic grafts.

An attempt has been made to reconstitute impaired cell-mediated immunity in 1 patient with indeterminate, 4 patients with borderline and 2 patients with polar lepromatous leprosy by grafting three thymus glands obtained from human fetuses of 14--19 weeks gestation. Most of these patients had severe ulcerative erythema nodosum leprosum (ENL) and were intolerant to dapsone. After thymus transplantation these patients were followed for 1 1/2 years. During this period, all conventional chemotherapy had been withdrawn. In most cases, there was dramatic improvement of the clinical condition, resolution of skin lesions, subsidence of ENL, clearance of bacteria from skin and reconstitution of several immunologic deficits; but late lepromin reactivity returned in none, which indicated permanent lose of resistance to Mycobacterium leprae.

Adult↗

PubMedDate not supplied

Toxoplasma gondii antibody in patients of lepromatous leprosy.

Sera from 140 lepromatous leprosy patients (test group) and 120 normal persons, who showed no clinical signs of acute or chronic toxoplasmosis (control group), were studied for the presence of Toxoplasma gondii antibody by indirect hemagglutination and indirect-immunofluorescent antibody tests. Both tests showed a high incidence of Toxoplasma antibody in the test group in comparison with the control group. IgM and IgG classes of antibody responses were observed in both the groups, which signified recent as well as past infections in them.

Adult↗

PubMedDate not supplied

Immunologic aspects of leprosy as related to leucocytic isoantibodies and platelet aggregating factors.

The incidences of various iso- and autoantibodies in a random population of 112 unselected leprosy patients is presented. Low titers of leucocytic isoantibodies and platelet aggregating factor were detected in the sera of a variable number of such patients. The leucoisoagglutinins were found in 8% of the sera of tuberculoid as well as lepromatous leprosy patients, whereas the leucoisocytotoxins were detected in a larger percentage of the lepromatous (40%) as well as tuberculoid (28%) cases. The platelet aggregating factors (PAF) were positive in 51.2% and 45% of lepromatous and tuberculoid cases respectively. Of the 21 positive sera for PAF, the antiplatelet factor by antihuman globulin consumption test could be demonstrated only in 66.6% and 50% of lepromatous and tuberculoid sera respectively. To study the frequencies of these newly detected antibodies or antibody-like factor and to compare their occurrences with other well-documented autoantibodies present in the sera of leprosy patients: cryoglobulins, antinucleoprotein antibody and thyroglobulin autoprecipitin were also studied in the sera of the same population of leprosy patients. It has been observed that the simultaneous occurrence of all these auto- and isoantibodies in the serum of one patient is a rare phenomenon. Leucocytic and platelet counts of these patients having antibodies against leucocytes and platelets were found to be within normal limits. Accordingly, it is suggested that the low levels of antileucocyte antibody and antiplatelet factor are probably harmless to the hosts. On the other hand, it is postulated that these antibodies may act as enhancing factors by being specifically adsorbed on the lymphoid cells, thus rendering them unresponsive to mitogenic stimulus in vitro. From these studies it seems that leprosy, especially the lepromatous type, is associated with some of the serological features suggestive of an autoimmune aberration.

Antibodies, Antinuclear↗

PubMedDate not supplied

Immunologic aspects of leprosy with special reference to the study of immunoglobulin E.

The serum levels of IgG, IgM, IgD and IgE have been determined in normal subjects, individuals suffering from ascariasis and filariasis, and in leprosy patients. Allergic and parasitic diseases were excluded in these normal subjects and in leprosy patients before they were taken for the study of their serum IgE. The circulating IgG was significantly raised in both tuberculoid and lepromatous forms of leprosy and also in filariasis; IgM was significantly elevated in only the lepromatous form of leprosy, ascariasis as well as in filariasis; while IgA was exclusively raised in both forms of leprosy. IgD was detected in the sera of more subjects with ascariasis and filariasis than in normal individuals and leprosy patients. The mean level of serum IgE in 35 normal Indian subjects was 1,025 I.U. per ml, 9 of them (25%) having serum IgE concentrations above 700 I.U. per ml. The highest mean level of serum IgE was found in ascariasis (7,328 I.U. per ml), followed by leprosy (5,180 I.U. per ml), and filariasis (4,244 I.U. per ml). Furthermore, no significant difference between the mean serum IgE levels of tuberculoid and lepromatous leprosy patients was observed. Although the rise of serum IgE level in these parasitic diseases, as well as in leprosy, was spectacular, the augmented synthesis of this unique class of immunoglobulins was not invariably present in all patients. The results have been discussed on the basis of recent ideas on immunoglobulin synthesis.

Adolescent↗

PubMedDate not supplied

Nitric oxide dependent killing of mycobacterium tuberculosis by human mononuclear phagocytes from patients with active tuberculosis.

In this study we have demonstrated that nitric oxide, the product of the arginine dependent pathway of human mononuclear phagocytes effectively kills the M.tuberculosis in-vitro. The release of reactive nitrogen intermediates was triggered by incubation with various proinflammatory cytokines namely IFN gamma,TNF-alpha and IL-1R. We have earlier shown that human mononuclear phagocytes can be induced to release nitric,oxide (NO) radicals which can kill tumour cells. In the present communication, by using colony forming assays we demonstrated that human mononuclear phagocytes can effectively kill M.tuberculosis by using a NO dependent pathway. Treatment of mononuclear phagocytes with L-arginine resulted in markedly increased killing activity whereas, by using NGMMA, an analogue of L-arginine, the cidal activity could be brought down to the basal level. These results clearly suggest that cytokines, particularly IFN-gamma, induced NO release and its reactive product with oxygen radical, peroxynitrite, could play an important role in the killing of M. tuberculosis by human mononuclear phagocytes. A significant production of interleukin-4 and interleukin-10, by the ex-vivo matured, untreated macrophages from the active tuberculosis patients indicate that regulation of cytokine network to encourage in situ/local production of nitric oxide may be useful in the management of pulmonary tuberculosis.

Journal Article↗

PubMedDate not supplied

T cell subpopulations in amoebic liver abscess.

BACKGROUND: Cellular immunity may play a major role in the pathogenesis of amoebic liver abscess but there is little data on the effect of treatment on T cell subpopulations in such patients. METHODS: We performed a prospective, controlled study of the T lymphocyte subpopulations in 17 patients with amoebic liver abscess before, and at 4 and 8 weeks after treatment with metronidazole (30 mg/kg/day). T4 and T8 cells were studied using monoclonal antibodies by the alkaline phosphatase anti-alkaline phosphatase staining technique. RESULTS: The mean T4 cell percentages in the acute stage of illness and at 4 and 8 weeks after treatment were 27, 26 and 27 respectively and the mean T8 cell percentages were 19, 24 and 29. The T4:T8 ratio at the acute stage was 1.7, and 1.1 and 1.2 at 4 and 8 weeks of therapy. The T4:T8 ratio at the acute stage did not differ significantly (p > 0.05) from that in the control group. However, at 4 and 8 weeks after therapy there was a significant increase (p < 0.05) in the T8 cells with no significant change in the T4 cells. CONCLUSION: We suggest that sensitization of the T8 cells occurs in patients with amoebic liver abscess in the later phase of the disease. This may be responsible for the elimination of the parasite from the human host.

Administration, Oral↗

PubMedDate not supplied

Serum complement profile in human leprosy and its comparison with immune complex diseases.

In the present study we have estimated the serum levels of early, middle, and distal complement components, e.g., Clq, C3, C4, C5, C8, and C9 along with C1-inactivator and CH50 in patients with tuberculoid and lepromatous leprosy and have compared these results with the levels in healthy subjects as well as with levels in patients with other immune complex diseases. We have also analyzed the cryoglobulins present in the sera of these patients; they consisted of either a single or mixed IgG, IgA, IgM or fibrinogen in most instances. The component C3 was found in only one sample. It appears that unlike lupus nephritis, in which complement is activated by direct path in which complement is activated by direct path in about 30% to 50% of leprosy patients, significant C3 complement consumption takes place primarily via the alternate pathway and is probably initiated by the aggregated immunoglobulins represented in cryoprecipitates. This is further supported by the study of serum factor B and its breakdown product (Ba) in these patients. The question of the role of the middle and distal complement components, such as C5, C8 and C9, during total hemolytic complement and C3 consumption in leprosy remains unanswered.

Complement C1 Inactivator Proteins↗

PubMedDate not supplied

Vaccine development in leprosy.

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Bacterial Vaccines↗

PubMedDate not supplied

Trace elements in the sera of leprosy spectrum.

Serum zinc, copper, calcium and magnesium levels were estimated by atomic absorption spectrophotometry in 56 leprosy patients comprising 14 BT, 12 BB, 11 BL and 19 LL. These findings were evaluated in comparison to 42 normal subjects serving as controls. A significant elevation of serum copper was recorded while reduction in zinc, calcium and magnesium was noted throughout the leprosy spectrum. The findings of our study are of considerable importance and need to be taken note of in the light of delineating these alterations to be the cause or effect of the disease.

Adolescent↗

PubMedDate not supplied

Immunologic aspects of lepromatous leprosy as related to the immunoglobulins of external secretions: salivary immunoglobulins.

A significant reduction in salivary immunoglobulins in lepromatous leprosy is recorded as compared to normal subjects. Saliva of undernourished subjects and patients with oral malignant tumors, which were studied as controls, showed an appreciable rise in IgA levels in both. It is suggested that impairment of T cell function, which is associated with lepromatous leprosy, is not responsible for the observed low level of salivary immunoglobulins in lepromatous leprosy.

Adult↗

PubMedDate not supplied

Serum histaminase in leprosy.

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Amine Oxidase (Copper-Containing)↗