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The half time of disappearance of dapsone and monoacetyl dapsone and the acetylator phenotype of the leprosy patients who harboured dapsone sensitive and dapsone resistant M. leprae was assessed in 27 subjects. Sixteen patients were rapid acetylators, five were slow and six were intermediate acetylators. The mean T 1 1/2 lives of dapsone (30.26 +/- 11.0) and monoacetyl dapsone (31.11 +/- 12.0) were also studied in the above patients. The percentage of different acetylators in both resistant and sensitive groups were similar showing no correlation between the emergence of drug resistance and the phenotype of the patient. The mean time of disappearance of DDS and MAD in the different acetylators did not show significant difference. The ratios of MAD/DDS in an individual at 3, 6 or 24 hours after the dose were similar. The mean T 1 1/2 lives of DDS and MAD in resistant and sensitive patients also showed no difference. Neither T 1 1/2 lives of DDS or MAD nor the acetylator phenotype seem to influence the emergence of dapsone resistance.

Gangliosides derived from tissues of normal and lepromatous armadillos were examined by thin-layer chromatography. The ganglioside patterns produced by the Mycobacterium leprae-infected tissues varied from that of the normal tissue. Although increased levels of several gangliosides were observed in the infected tissues, there was an apparent preferential increase in GM3 gangliosides as determined by column chromatography and enzymatic hydrolysis.

The cutaneous innervation is now known to contain neuropeptides including substance P (SP) and calcitonin gene-related peptide (CGRP) in sensory nerves, and vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY), principally in autonomic nerves. Skin biopsies from 100 leprosy patients and equivalent areas from 50 non-leprosy controls were fixed in p-benzoquinone solution for immunofluorescence staining and in Bouin's fluid for classification of leprosy type. Antisera to the neural markers, neurofilaments, and protein gene product 9.5 (PGP 9.5), and to neuropeptides were used. Cutaneous nerves and nerve endings immunoreactive for neuropeptides, neurofilaments, and PGP 9.5 were seen in all non-leprous control cases. In leprosy, PGP 9.5- and neurofilament-immunoreactive nerve fibres were seen in all 14 cases of the indeterminate (early) type and in the majority (33/43) of lepromatous cases, but in a smaller proportion (15/43) of tuberculoid cases. Neuropeptide immunoreactivity was seen in only 2/14 of the indeterminate leprosy specimens and was completely absent in other types. This early disappearance may be of diagnostic significance. Thus, cutaneous sensory and autonomic dysfunctions in leprosy are well reflected by changes in nerve fibres and neuropeptides.

The histological examination and the chemical estimation of clofazimine in the organs removed at autopsy of a patient receiving the drug indicated the accumulation of the drug in the organs of the reticulo-endothelial system and those having a large number of macrophages. The clofazimine levels in the skin from patients receiving the drug and those in whom the drug had been stopped for different periods of time were compared. The skin levels of clofazimine bore a direct relationship to the size of the granuloma. A slow elimination of the drug from the tissues was indicated by the presence of traces of the skin tissue even 1-2 years after stopping the drug. The clinical implication of these findings are discussed.

Fifteen untreated leprosy patients were given rifampicin and dapsone for seven days, and then rifampicin, dapsone and clofazimine for seven days. Concentrations of rifampicin and dapsone were estimated in timed plasma specimens and in 24 h urine specimens on days 7 and 14. No significant differences in the pharmacokinetics of rifampicin and dapsone were observed between the two occasions of sampling.

We examined the generation of active oxygens (O2-, H2O2, and OH X ) and the superoxide dismutase (SOD) activity of polymorphonuclear leukocytes (PMNs) and monocytes from 14 leprotic patients manifesting a bacillary index above 2.2. Patients with disease of more than 4 years in duration showed significantly enhanced SOD activity and a decrease in O2- and OH X production. The antileprotic agent, clofazimine, significantly increased the generation of OH X in a dose-dependent manner, with a subsequent decrease in H2O2, but had no effect on the SOD activity of the PMNs and monocytes. In medium containing FeSO4 or Fe2+-EDTA, the drug elevated OH X production markedly further. Phagocytic SOD in PMNs and monocytes of leprotic patients was both host and bacillus derived, because the presence of cyanide, to which human-derived cuprozinc SOD is susceptible, did not completely abrogate SOD activity. The difficulty in treating leprosy may be partly ascribable to decreased phagocytic OH X generation, which in leprosy patients is apparently due to the uptake of Hansen bacillus-derived SOD. Clofazimine may be effective in leprosy by chelating Fe2+, with the resultant potentiation of the catalyzing activity of Fe2+ in the Haber-Weiss reaction increasing OH X formation from H2O2.

Macrophages from lepromatous leprosy patients specifically show reduced protein synthesis in the presence of M. leprae. They also produce, as a result of interaction with M. leprae, factor(s) that reduce protein synthesis in normal macrophages as well as block lymphocyte transformation in normal leukocyte cultures in the presence of M. leprae as the antigen. These observations implicate a defective macrophage system in lepromatous leprosy patients.

Electron- and light microscopic analyses were conducted on leprosy skin biopsies relative to the origin of hyaluronic acid, which has previously been observed to be distributed inversely in ratio to the degree of cell- mediated immunity. The present study investigated the subcellular localization of hyaluronic acid and its degrading enzyme in various types of leprosy. Hyaluronic acid in some lepromatous leprosy cases was shown to be accumulated in the limiting membranes of the phagosomes of lepra cells and Myco-bacteria leprae have beta-glucuronidase which plays a role in the degradation of hyaluronic acid. Contrariwise, in tuberculoid leprosy, beta-glucuronidase was detected in the lysosomes of epithelioid cells and giant cells. This result suggests that the origin of hyaluronic acid is in histiocytes and at the same time it might suggest that M. leprae is in competition with enzymes of epithelioid cells for hyaluronic acid, whereas reduced or absent beta-glucuronidase in lepra cells enable bacilli to utilize the AMPS as a nutrient.

Blood xylose concentrations were measured at 60, 90 and 120 min after 25 xylose was given orally in 33 well-nourished Papua New Guinean in-patients at Port Moresby; 12 had lepromatous (group A) and seven non-lepromatous (group B) leprosy, and 14 were controls (group C). Differences between mean xylose concentrations were not significant at any time interval. Three patients (two in group A and one in group B) had 90 min xylose concentrations less than 2.0 mmol l-1. There was no association between xylose concentration and current therapy. Leprosy does not impair small-intestinal absorptive function; it therefore differs from other chronic infections, in which there is xylose malabsorption.

A characteristic mycobacterial wax, phthiocerol dimycocerosate, has been isolated from liver of armadillos experimentally infected with Mycobacterium leprae. The structure of this wax is generally similar to that produced by Mycobacterium tuberculosis, but the homologous phthiocerol and the mycocerosic acid components from M. leprae are significantly different from those of M. tuberculosis.

3H-leucine uptake by macrophages from swiss white and C57BL mice before and after M. leprae infection was studied. A depression in 3H-leucine uptake after infection was observed only in swiss white mice. 3H-leucine uptake was also studied in blood derived macrophages from normals, and LL and TT patients. A depression was obtained in 3H-leucine uptake after M. leprae infection in macrophages from LL patients.

Croystat sections of dermal lesions from 33 untreated patients with leprosy were studied by indirect immunofluorescence using monoclonal antibodies to human fibronectin. Macrophages in borderline (BL) and lepromatous (LL) leprosy showed intense staining with antifibronectin antibodies. In the tuberculoid lesions cells of the mononuclear phagocyte series in an epithelioid cell granuloma stained for fibronectin. The lymphocytes surrounding these granulomas also showed the presence of fibronectin. These results suggest that the granuloma of leprosy consists of macrophages expressing fibronectin and the lymphocytes in the lesion also appear to express this protein. In six borderline cases, the sub epidermal collagen band showed intense staining with antifibronectin antibodies. In addition, the distribution of Ia-like antigens and fibronectin was studied on the plastic adherent cells obtained from peripheral blood of 11 untreated patients with leprosy. Results indicate that higher percentage of adherent cells from lepromatous patients express fibronectin in comparison to adherent cells from tuberculoid patients or controls. However, no difference was observed in the expression of the Ia-like antigens by the adherent cells, from these patients.

On the basis of the efficacy of the available agents, the World Health Organization has recommended only 4 drugs for combined chemotherapy of leprosy: rifampicin, dapsone, clofazimine and ethionamide/prothionamide. Thiacetazone and isoniazid are also used to a lesser extent by some physicians. Pyrazinamide may find a place in treating 'persister' bacilli. Dapsone is absorbed slowly after oral administration. Peak plasma drug concentration is reached at about 4 hours; absorption half-life is 1.1 hours; elimination half-life is about 30 hours. Oral availability is around 90%. Dapsone is approximately 70% protein-bound, while its monoacetylated metabolite is almost entirely bound. Dapsone crosses the placenta and is excreted into breast milk. It is metabolised via acetylation and N-hydroxylation, but acetylation polymorphism has no effect on dapsone handling by leprosy patients. Dapsone penetrates into sciatic nerves of experimental animals but its presence has not been demonstrated in Schwann cells. Oral doses of rifampicin are rapidly and completely absorbed. The bioavailability is greater when the drug is given before meals; peak concentrations occur at 1 to 2 hours. 80 to 90% of rifampicin is bound to plasma proteins, and the drug is found in saliva, cerebrospinal fluid and breast milk. Its main metabolite, desacetyl rifampicin, also exhibits antimycobacterial activity in tuberculosis. Rifampicin induces its own metabolism, as well as that of dapsone and steroids. Absorption of dapsone and rifampicin is reported to be reduced in leprosy patients. Clofazimine has been in use in leprosy treatment since 1960. In higher doses it exerts an anti-inflammatory action which is useful in treating leprosy patients in reaction. Oral absorption of the drug is slow and dose-dependent; faecal excretion also increases with dose. Single- and multiple-dose studies have shown a plasma half-life of around 10 days. Bioavailability of the drug is higher when given with food than when fasting; the peak plasma concentration occurs at 4 to 8 hours when the drug is administered with breakfast. After absorption, the drug is thought to circulate in protein-bound form, accounting for the fact that it is deposited in various tissues. Uneven distribution and prolonged retention in the tissues are special features of clofazimine metabolism. One unconjugated and 2 conjugated metabolites have been detected in urine, and the urinary excretion of both the parent compound and its metabolites is around 1% of the dose.(ABSTRACT TRUNCATED AT 400 WORDS)

A phenolic glycolipid was obtained in high amounts (2% of dry weight) from Mycobacterium leprae isolated from infected armadillo liver. Infrared and nuclear magnetic resonance spectroscopy showed that it is closely related to "mycoside A" from Mycobacterium kansasii and is therefore a glycosylphenolic phthiocerol diester. The crucial difference between the two products is in the composition of the attached trisaccharide. Gas-liquid chromatography-mass spectroscopy showed that the product from M. kansasii is composed of 2,4-di-O-methylrhamnose, 2-O-methylrhamnose, and 2-O-methylfucose, whereas that from M. leprae contains 2,3-di-O-methylrhamnose, 3-O-methylrhamnose, and 3,6-di-O-methylglucose. The distinct composition of the oligosaccharide segment of the glycolipid from M. leprae may make it useful for the chemical and serological differentiation of this organism from other mycobacteria. Surprisingly large quantities (2.2 mg/g of dry liver) of the glycolipid were also found in infected liver residue freed of M. leprae, suggesting that it may be responsible for the electron-transparent "foam" surrounding the organism in infected lepromatous tissue.

A method is described for the extraction of mycolic acid from lepromatous leprosy tissues and from tuberculous tissues and its identification by thin layer chromatography. Verification of the mycolic acid extracted and separated by thin layer chromatography was accomplished by infrared spectroscopy. Although the presence of mycolic acid in tissues is not, in itself, diagnostic for leprosy, its demonstration in biopsy tissues might be a useful additional qualitative test if used in conjunction with clinical evidence of the disease.

Cytochrome oxidase (CCO), peroxidase, succinic dehydrogenase (SDG) and NADH-diaphorase were studied electron-cytochemically in leprous macrophages (LM) of granulomas of patients suffering from lepromatous leprosy. The LM peroxidase activity and location differed, this affecting the completeness of M. leprae phagocytosis. High CCO activity in LM cytoplasm was not a factor essentially influencing M. leprae disintegration. SDG and NADH-diaphorase, locating predominantly in membraneous structures of M. leprae, show low activity in LM cytoplasm.

The physiologic states of Mycobacterium leprae isolated from patient biopsies were studied using single cell mass spectrometry by laser microprobe mass analysis (LAM-MA) and ATP bioluminescence assay. The changes in the physiologic state of M. leprae after the patients had been treated with dapsone (DDS) monotherapy were also studied. The shift of the low intracellular Na+, K+-ratio of untreated M. leprae cells to higher values under DDS therapy, as measured from a limited number of single bacteria, correlates with a decrease in the ATP content. Further information on the influence of the drug could be drawn from the multivariate analysis of mass fingerprints of the organic matrix of the cells. Evidence is provided that the combination of the measurement of the intracellular cation ratios and of the mass fingerprint analysis could give fast answers to the question of drug resistance and to the persister hypothesis. The ATP bioluminescence assay and the single cell mass analysis should be alternatives to the mouse foot pad test.

Uniform accumulation of acid mucopolysaccharides in all types of leprosy lesions was seen, except late tuberculoid lesions which showed the accumulation only at the periphery. Absence of acid mucopolysaccharides was significant in well formed epithelioid granulomas and in giant cells of late tuberculoid cases. Generally a progressive decrease with advancing chronicity of the disease was noted. The dermal zone without any cellular infiltrate showed abundant acid mucopolysaccharides in comparison to those areas having inflammatory cell infiltrate in 70.83% of LL, 42.86% of BL, 33.3% of BB, 40.0% of BT, and 13.51% of TT cases. In Indeterminate cases the distribution was same to that of control cases. Testicular hyaluronidase digestion established that hyaluronic acid constituted the main bulk of acid mucopolysaccharides. The possible source of hyaluronic acid is discussed.

Dapsone (DDS) in urine of 250 leprosy patients collected on surprise visits were screened by simple paper spot, tile tests and sensitive Enzyme linked immunosorbent assay (ELISA) and Haemagglutination inhibition (HI) tests. The urinary DDS concentration as well as DDS/C ratios were also studied. Simultaneously, 50 microliter of blood was collected from each of these patients and its dapsone content was estimated by HPLC. Urine samples with means of 25 to 30 micrograms/ml DDS and 55-64 micrograms/mg DDS/C ratios were found to give positive tests by any of the above screening procedures, while their mean blood DDS concentration was found to be 0.91 microgram/ml. The corresponding values for those specimens giving negative tests were 3.8 to 5.7 micrograms DDS per ml and 9 to 13 micrograms/mg DDS/C ratio. The blood DDS concentration in this group was ranging from 0.16 to 0.18 micrograms/ml. The findings are discussed in relation to their metabolic significance and their application in a leprosy control programme.

Skin and serum zinc measurements have been made in patients with leprosy with and without trophic skin ulceration and in several other groups. Serum zinc concentrations were decreased in leprosy irrespective of the presence or absence of skin ulceration. Serum zinc concentrations in leprosy were also unrelated to smears positive for Mycobacterium leprae and to the clinical type of leprosy. Since a decrease of the serum zinc was also found in patients with dermatitis herpetiformis and pulmonary tuberculosis it seems likely that the decreased serum zinc in leprosy is a nonspecific metabolic consequence of chronic skin and internal disease. The mean skin zinc concentration in leprosy did not differ significantly from the corresponding value in control subjects, the lack of agreement between serum and skin concentrations being possibly related to the presence of nonexchangeable keratin-bound zinc in skin. Though the clinical significance of lowered serum zinc concentrations in leprosy is uncertain therapeutic trials of zinc treatment in leprosy with trophic skin ulceration seem justifiable.

Desoxyfructo-serotonin (DFS) being a naturally occurring metabolite, which, like serotonin, has its origin in tryptophane in the food, one can ask about the role of nutrition in leprosy. The unique situation, that a human metabolite shows antileprosy activity, confirmed in vitro and in vivo, makes it possible to develop a "build in" antileprosy therapy. This is now realised through a so-called "Anti-Leprosy Nutriment" (NAL). The effectiveness of this diet was confirmed by the fact, that a daily dose of 0.5 g NAL per mouse has a similar effect, like 20 mg/kg body weight Dapsone per day in the conventionnal mouse foot-pad test. The biosynthesis of DFS in man has been demonstrated by high performance liquid chromatography (HPLC), spectrofluorometry and mass spectrometry. The activity of NAL (rich in tryptophane, unsaturated fatty acids and glucose) is due to an increased biosynthesis of DSF. The latter may be considered as a "physiological protecting agent" against leprosy. This type of food may play a role in the prevention of leprosy in endemic area.

There is ample evidence that the human acetylator phenotypes are associated with drug induced phenomena. It is principally the slow acetylators who exhibit toxic adverse effects because of their relative inability to detoxify the original drug compounds. In rare instances, however, it is the rapid acetylators who are at a disadvantage. In the matter of association of spontaneous disease with either acetylator phenotype, there are two groups of disorders to consider. First, disorders in which carcinogenic amines are known to be an aetiological factor. This is because these amines are substrates for the polymorphic N-acetyltransferase activity and hence there is a possible rational basis for searching for an association. Secondly, other disorders where searches for associations are based more on hunches. In the first group there is a definite statistical association between cancer of the bladder and the slow acetylator phenotype. In prevalence studies the slow phenotype is 39% more associated with bladder cancer than is the rapid phenotype. On the basis of the evidence now available it is not possible to say whether this association is because slow acetylators develop the disease more frequently or whether they survive longer. In the second group the relevant studies show (1) a greatly increased prevalence of slow acetylators in Gilbert's disease; (2) a confirmed association between the rapid acetylator phenotype and diabetes; (3) a possible association between the rapid acetylator phenotype and breast cancer; (4) a possible association between the slow acetylator phenotype and leprosy in Chinese patients; (5) an earlier age of onset of thyrotoxicosis (Graves' disease) in slow acetylators than in rapid acetylators; (6) no evidence of an association between either phenotype and spontaneous systemic lupus erythematosus.

Schwann cells that contain M. leprae fail to incorporate DNA precursor, indicating blockage of DNA synthesis. Such a block could lead to no proliferation of Schwann cells, an essential requirement for successful association with axons and consequent myelination.

Pharmacokinetics of aspirin and chloramphenicol was studied in 16 normal and 16 patients suffering from leprosy. A significant increase (p less than 0.05) in the elimination half-life of chloramphenicol was observed before and after dapsone treatment in leprotic patients as compared with the normal volunteers, while no significant difference was observed in any of the pharmacokinetic parameters with aspirin.

Monocyte-derived macrophages from 14 patients with lepromatous leprosy respond to rIFN-gamma with an enhanced secretion of H2O2 in a fashion similar to that of cells obtained from normal donors. The activation is not dependent on the cutaneous bacterial index, the length of treatment, or the stage and activity of the disease. H2O2 release can be triggered in these cells both by phorbol myristate acetate and by intact irradiated Mycobacterium leprae. Uptake of M. leprae by both normal donors' and patients' macrophages is proportional to the number of bacilli added. Prior ingestion of M. leprae does not interfere with the ability of macrophages to respond to IFN-gamma by the production of oxygen intermediates. We conclude that the immune defect in lepromatous leprosy probably results from a lack of response to M. leprae by the patients' T cells rather than an inability of mononuclear phagocytes to respond to IFN-gamma.

Phenolic glycolipid (PGL)-I, a Mycobacterium leprae-specific antigen currently used for serodiagnosis of preclinical leprosy, has thus far not been localized subcellularly in leprosy bacilli and their host cells. In this study, we developed an immunogold-labeling technique for qualitative identification of PGL-I sites in glutaraldehyde-osmium-fixed and Araldite-embedded M. leprae and host macrophages in human skin biopsies. Such "hard-fixed," plastic-embedded skin and nerve biopsies from patients with varying cell-mediated immunity to leprosy are amply available worldwide. Our method involves etching of plastic sections with H2O2, incubation with swine serum to eliminate nonspecific labeling, and long (22 hr) incubation at room temperature with monoclonal antibodies to PGL-I. Gold labeling was seen predominantly on cell walls of M. leprae, in vacuolar spaces of bacillated phagolysosomes, and occasionally on the cytoplasm and cell membrane of M. leprae. Host macrophage cytoplasm was labeled very infrequently. This technique allows studies on possibly persisting antigenic PGL-I in multibacillary leprosy patients during or after multidrug therapy. The method may also prove useful for subcellular localization of specific bacterial lipids in other mycobacterial diseases, including tuberculosis.

Mycobacterial antigens which play a major role in humoral and cell-mediated immune recognition are related to proteins which are induced in response to stress stimuli. The potential involvement of stress-induced proteins in infectious disease and in autoimmune responses is discussed.

Phenolic glycolipid-I, a marker lipid of Mycobacterium leprae, was isolated from skin biopsies obtained from untreated lepromatous leprosy patients by silicic acid and florisil column chromatography and purified by thin layer chromatography. Tissues with varying bacillary loads were analysed for their phenolic glycolipid content. A good correlation was observed between the bacillary population of the tissues and the phenolic glycolipid content.

Thin-layer chromatography was used to compare lipid extracts from lepromatous skin biopsies with those from normal skin and from Mycobacterium leprae purified from armadillo spleen. Several lipids were found in infected skin which were absent from normal skin but corresponded to lipids present in the purified M. leprae. These included mycolic acids, a 6-deoxyhexose-containing lipid (glycolipid I) and a wax ester (possibly related to the Mycobacterium tuberculosis wax, phthiocerol dimycocerosate). Unlike Mycobacterium lepraemurium, M. leprae contained no C-type mycosides. In terms of lipid profile, M. leprae from armadillo spleen showed the same characteristics as bacilli from human skin samples. Quantitative analysis of mycobacterial lipids in lepromatous skin biopsies indicated that their concentrations were much higher than would be predicted from the number of acid-fast bacilli present. Accumulation of lipid debris from dead M. leprae could provide a protective environment in infected cells for remaining viable bacilli.

Lysozyme concentrations have been estimated in 47 patients with lepromatous leprosy and in 50 healthy people by a single radial immunodiffusion technique using monospecific antiserum against human lysozyme. In healthy people the mean tear lysozyme concentration was 1.34 mg/ml. In leprosy patients the mean tear lysozyme concentration was 1.0 mg/ml. Anterior uveitis per se did not appear to alter the lysozyme concentration in tears.

In order to determine the suitability of the armadillos as a model of human leprosy for chemotherapeutic studies, especially in evaluating newer anti-leprosy drugs, uninfected Armadillos were used to study the metabolic disposition of DDS. Serum DDS levels ranged from 500 ng/ml at 3 hours to 13 ng/ml at 96 hours after intravenous administration of DDS (1 mg/kg). In an ad libitum feeding trial of DDS it was found that the level of serum DDS varied according to the dose of DDS, and even at a dose of 0.0001%, the animals maintained MIC of DDS against M. leprae. Finally, it was demonstrated that armadillos acetylate DDS to MADDS and 7-9% of DDS is acetylated by armadillos.

Beta2-glycoprotein I typings on 152 healthy Germans and 150 patients with atopic diseases did not show any differences in the serum protein concentrations or in the phenotype and gene frequencies. Compared to these German samples, Philippinos (n = 88) as well as healthy Negroes from South Africa (n = 192) revealed statistically significant lower concentrations of this serum protein. They differ also from the Germans with regard to phenotype and gene frequencies. A most striking result was found in the comparison of healthy and leprous Negroes (n = 250) from South Africa. In these, quite different and statistically significant beta 2-Glycoprotein I concentrations, respectively, phenotype and gene frequencies were seen, which may be due to this disease. The possible reasons for these observations as well as for the observed population differences are discussed.

We have herewith examined the characteristics of circadian rhythms in patients with lepromatous leprosy, active or inactive, allowing a comparison with corresponding properties of rhythms in healthy subjects mapped earlier. Group results were illustrated by cosinor plots, produced directly on microfilm by computer. Eventually such reference standards in the form of cosinors, among other displays, notably of waveform, may be individualized and carried on a person's health record. Such a quantitative assessment of an individual's rhythms in health may serve for rigorous comparison with any changes accompanying increased susceptibility or occult or overt disease.

The responsiveness of 25 leprosy patients to an in vitro correlate of cell-mediated immunity to M. leprae antigen, (the production of Y-IFN by peripheral blood mononuclear cells) was compared to their response to skin tests routinely used to evaluate cell-mediated immunity to a number of antigens including M. leprae. The results indicate that among the polar lepromatous patients (LL) there was a clear correlation between low responses in the in vitro assay (Y-IFN production), negative skin test to the specific antigen (Mitsuda reaction) and low responses to skin tests to a related antigen (PPD). There was no correlation in the other clinical groups with skin tests to other unrelated antigens.

Because the accumulation and activation of mononuclear phagocytes are critical to the host response to intracellular microbial pathogens, we evaluated mechanisms of peripheral monocyte leucotactic regulation in leprosy. Plasma from 53 of 67 patients was found to inhibit the locomotion of normal human monocytes. Neither the prevalence nor the magnitude of plasma leucotactic inhibitory activity correlated with disease histology or duration, type or duration of chemotherapy, or history of erythema nodosum leprosum. Plasma leucotactic inhibitory activity resided principally in a non-immunoglobulin, cell-directed inhibitor of 230,000 daltons molecular weight. Fractionation of plasma from patients with lepromatous leprosy revealed an additional, immunoglobulin-containing inhibitor of approximately 400,000 daltons weight, possibly an IgG-IgA immune complex. Production of leucotactic inhibitors by unstimulated and concanavalin A-stimulated peripheral mononuclear cells was normal; however, cutaneous explants from these patients spontaneously produced the 230,000 dalton leucotactic inhibitor in vitro. The ability of the lesions of leprosy to impede monocyte traffic may be an important pathogenetic mechanism.