03167nas a2200361   4500000000100000008004100001260001600042653001000058653002400068653003200092653001400124653003000138653001100168653001100179653003700190653001500227653002600242653001200268653001600280653000900296653001600305653001400321653002500335653001400360100001600374700001400390700001300404245008200417300001100499490000800510520227300518022001402791       1984                            d  c1984 Mar 0110aAdult10aBiological Products10aBlood Bactericidal Activity10aCytokines10aCytotoxicity, Immunologic10aFemale10aHumans10aImmunologic Deficiency Syndromes10aLegionella10aLegionnaires' Disease10aleprosy10aLymphocytes10aMale10aMiddle Aged10aMonocytes10aMycobacterium leprae10aThymidine1 aHorwitz M A1 aLevis W R1 aCohn Z A00aDefective production of monocyte-activating cytokines in lepromatous leprosy.  a666-780 v1593 a<p>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.</p>  a0022-1007