Defective production of monocyte-activating cytokines in lepromatous leprosy. 1984

M A Horwitz, and W R Levis, and Z A Cohn

We have examined the capacity of monocytes from patients with leprosy to undergo activation and the capacity of mononuclear cells from these patients to incorporate [3H]thymidine and produce monocyte-activating cytokines. Monocytes from patients with either lepromatous or tuberculoid leprosy were activated by concanavalin A (Con A)-induced mononuclear cell supernatants generated from the leukocytes of a normal person. Monocytes activated by these supernatants strongly inhibited L. pneumophila multiplication, and the degree of inhibition was comparable in both groups of patients. Mononuclear cells from patients with either form of leprosy responded comparably to Con A with vigorous [3H]thymidine incorporation. Mononuclear cells from patients with tuberculoid leprosy also vigorously incorporated [3H]thymidine in response to M. leprae antigens. In contrast, mononuclear cells from patients with lepromatous leprosy did not exhibit significant [3H]thymidine incorporation in response to M. leprae antigens. The capacity of mononuclear cells to generate monocyte-activating cytokines generally paralleled their capacity to incorporate [3H]thymidine in response to Con A and M. leprae. Mononuclear cells from patients with either form of leprosy responded to Con A with the production of cytokines (supernatants) able to activate normal monocytes, expressed by inhibition of L. pneumophila multiplication. However Con A-induced supernatants from patients with lepromatous leprosy were less potent than Con A-induced supernatants from patients with tuberculoid leprosy. Mononuclear cells from patients with tuberculoid leprosy responded to M. leprae antigens with the production of potent monocyte-activating supernatants. In contrast, mononuclear cells from patients with lepromatous leprosy did not produce monocyte-activating cytokines in response to M. leprae antigens. These studies support the hypothesis that the immunological defect in lepromatous leprosy results from a failure to activate mononuclear phagocytes rather than from an intrinsic inability of these cells to be activated. We suggest that the failure to activate mononuclear phagocytes stems from defective production of monocyte-activating cytokines in response to M. leprae antigens.

UI MeSH Term Description Entries
D007153 Immunologic Deficiency Syndromes Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral. Antibody Deficiency Syndrome,Deficiency Syndrome, Immunologic,Deficiency Syndromes, Antibody,Deficiency Syndromes, Immunologic,Immunologic Deficiency Syndrome,Immunological Deficiency Syndromes,Antibody Deficiency Syndromes,Deficiency Syndrome, Antibody,Deficiency Syndrome, Immunological,Deficiency Syndromes, Immunological,Immunological Deficiency Syndrome,Syndrome, Antibody Deficiency,Syndrome, Immunologic Deficiency,Syndrome, Immunological Deficiency,Syndromes, Antibody Deficiency,Syndromes, Immunologic Deficiency,Syndromes, Immunological Deficiency
D007875 Legionella Gram-negative aerobic rods, isolated from surface water or thermally polluted lakes or streams. Member are pathogenic for man. Legionella pneumophila is the causative agent for LEGIONNAIRES' DISEASE.
D007877 Legionnaires' Disease An acute, sometimes fatal, pneumonia-like bacterial infection characterized by high fever, malaise, muscle aches, respiratory disorders and headache. It is named for an outbreak at the 1976 Philadelphia convention of the American Legion. Legionella pneumophila Infections,Infections, Legionella pneumophila,Legionnaire Disease,Pontiac Fever,Disease, Legionnaire,Disease, Legionnaires',Fever, Pontiac,Infection, Legionella pneumophila,Legionella pneumophila Infection,Legionnaire's Disease,Legionnaires Disease
D007918 Leprosy A chronic granulomatous infection caused by MYCOBACTERIUM LEPRAE. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. Hansen's Disease,Hansen Disease
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D009166 Mycobacterium leprae A species of gram-positive, aerobic bacteria that causes LEPROSY in man. Its organisms are generally arranged in clumps, rounded masses, or in groups of bacilli side by side.
D001770 Blood Bactericidal Activity The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST. Activities, Blood Bactericidal,Activity, Blood Bactericidal,Bactericidal Activities, Blood,Bactericidal Activity, Blood,Blood Bactericidal Activities

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