02890nas a2200457 4500000000100000008004100001260001600042653001000058653001100068653004100079653002000120653001100140653002200151653002400173653002000197653002100217653002100238653001200259653000900271653001600280653001400296653002500310653002500335653000900360653001800369100001500387700001300402700001400415700001300429700001500442700001600457700001200473700001700485700001700502700001300519245011300532300000900645490000800654520175600662022001402418 1986 d c1986 Jul 0310aAdult10aFemale10aHistocompatibility Antigens Class II10aHLA-DR Antigens10aHumans10aHydrogen Peroxide10aIn Vitro Techniques10aInjections, Jet10aInterferon-gamma10aLangerhans Cells10aleprosy10aMale10aMiddle Aged10aMonocytes10aMycobacterium leprae10aRecombinant Proteins10aSkin10aT-Lymphocytes1 aNathan C F1 aKaplan G1 aLevis W R1 aNusrat A1 aWitmer M D1 aSherwin S A1 aJob C K1 aHorowitz C R1 aSteinman R M1 aCohn Z A00aLocal and systemic effects of intradermal recombinant interferon-gamma in patients with lepromatous leprosy. a6-150 v3153 a

Evidence that interferon-gamma may be a physiologic macrophage-activating factor, and that macrophage activation may be defective in lepromatous leprosy, led us to test the effects of intradermal injection of low doses of recombinant interferon-gamma in six patients with this disease. Interferon-gamma, 1 or 10 micrograms, was administered daily by jet gun for three days into a single cutaneous lesion. A biopsy specimen was taken from the injection site on the sixth study day and compared with specimens obtained previously from a site where no injection had been made or where excipient alone had been injected in the same way as the interferon. Interferon-gamma elicited local effects similar to certain features of delayed-type hypersensitivity reactions or tuberculoid leprosy, including induration, T-cell and monocyte infiltration, keratinocyte proliferation, diminution of epidermal Langerhans cells, and dermal and epidermal cell HLA-DR (Ia) antigen expression. At some of the sites of interferon-gamma injection, there was also an apparent decrease in acid-fast bacilli. Before treatment, monocytes from patients with lepromatous leprosy released 48 percent as much hydrogen peroxide as did monocytes from controls in response to phorbol myristate acetate, and 36 percent as much as those from controls in response to Mycobacterium leprae. When recombinant interferon-gamma was injected, these responses became normal. No toxic effects were observed. These observations suggest that interferon-gamma can mediate certain manifestations of delayed-type hypersensitivity or cell-mediated immunity in vivo, and that recombinant interferon-gamma should be tested for possible therapeutic effects in certain nonviral infectious diseases.

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