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| BIDIRECTIONAL EFFECTS OF CYTOKINES ON THE GROWTH OF MYCOBACTERIUM-AVIUM WITHIN HUMAN MONOCYTES |
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| Author(s): SHIRATSUCHI H, JOHNSON JL, ELLNER JJ |
| Source: JOURNAL OF IMMUNOLOGY Volume: 146 Issue: 9 Pages: 3165-3170 Published: MAY 1 1991 |
| Times Cited: 95 References: 54 |
| Abstract: Certain cytokines including IFN-gamma possess macrophage-activating factor activity that enhances the ability of these effector cells to destroy intracellular pathogens. A panel of recombinant and highly purified human cytokines was screened to detect this effect on the activation of human monocytes to kill Mycobacterium avium in an in vitro model. Peripheral blood monocytes obtained from 15 healthy donors were precultured for 2 days before infection. Monocytes were infected with two strains of M. avium, one AIDS-associated and relatively avirulent strain (86m2096), and the other a non-AIDS-associated isolate that demonstrated consistent and rapid growth in cultured human monocytes (LR114F). The effects of recombinant and purified human cytokines on M. avium infection were assayed by determining CFU of M. avium in lysates of infected monocytes after 0, 4, and 7 days of culture. After infection, monocytes were cultured in medium alone or continuously in the presence of the following cytokines: IL-1-alpha, IL-1-beta, IL-2, IL-3, IL-4, IL-6, IFN-gamma, granulocyte-macrophage-CSF, or macrophage-CSF. In some experiments, cultures were performed in the presence of indomethacin (IM) in addition to cytokines. Culture in the presence of rIFN-gamma was associated with a decrease in mycobacterial growth within human monocytes. The combination of 300 U/ml of IFN-gamma plus 1-mu-g/ml of IM was associated with a 10-fold decrease (p < 0.01) in intracellular growth of the virulent strain (LR114F) compared with unstimulated cultures. No other cytokine or combination of a cytokine with IM inhibited the intracellular growth of either strain of M. avium in human monocytes. Rather, several cytokines enhanced the intracellular growth of M. avium. IL-3, IL-6, and macrophage-CSF increased the growth of one, and IL-1-alpha of both strains of M. avium tested. IL-1-alpha and IL-6 also induced M. avium growth in tissue culture medium without monocytes. These studies indicate bidirectional effects of cytokines on intracellular parasitism that may influence the outcome of M. avium infection. |
| Document Type: Article |
| Language: English |
Addresses:
1. CASE WESTERN RESERVE UNIV, SCH MED, DEPT MED, DIV INFECT DIS, 2109 ADELBERT RD, CLEVELAND, OH 44106 USA
2. UNIV HOSP CLEVELAND, CLEVELAND, OH 44106 USA
3. VET ADM MED CTR, CLEVELAND, OH 44106 USA |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Immunology |
| IDS Number: FJ133 |
| ISSN: 0022-1767 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |