{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:17:36Z","timestamp":1792131456982,"version":"4.4.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[1998,9,1]],"date-time":"1998-09-01T00:00:00Z","timestamp":904608000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[1998,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Increased production of tumor necrosis factor alpha (TNF-\u03b1) appears to play an important role in the progression of human immunodeficiency virus disease. One treatment strategy being explored is the use of TNF-\u03b1 inhibitors. TNF-\u03b1 also appears to be important in conferring resistance to infections, and the inhibition of this cytokine may exacerbate the emergence of opportunistic pathogens, such as<jats:italic>Mycobacterium avium<\/jats:italic>complex (MAC). The present study examines the possibility that inhibition of TNF-\u03b1 will increase the progression of disease in mice infected with MAC. C57BL\/6 beige (<jats:italic>bg\/bg<\/jats:italic>) mice have been shown to be highly susceptible to infection with MAC and are routinely used for testing of antimycobacterial drugs. However,<jats:italic>bg\/bg<\/jats:italic>mice are known to exhibit impaired phagocyte and natural killer cell function. Since these cell types are important sources of TNF-\u03b1, the susceptibility of the<jats:italic>bg\/bg<\/jats:italic>strain to infection with MAC was compared with those of the heterozygous (<jats:italic>bg<\/jats:italic>\/+) and wild-type (+\/+) strains of C57BL\/6 mice. The susceptibilities of the<jats:italic>bg\/bg<\/jats:italic>and<jats:italic>bg<\/jats:italic>\/+ strains of mice infected with MAC were found to be comparable. The +\/+ strain was the least susceptible. Mycobacterial burden and serum TNF-\u03b1 levels increased over time in all the strains of mice tested. The<jats:italic>bg<\/jats:italic>\/+ strain of C57BL\/6 mice was then chosen to measure the activity of TNF-\u03b1 antagonists. Treatment with dexamethasone decreased serum TNF-\u03b1 levels and increased mycobacterial burden. Treatment with anti-TNF-\u03b1 antibody or pentoxifylline did not significantly alter serum TNF-\u03b1 levels but increased mycobacterial burden. Treatment with thalidomide neither consistently altered mycobacterial burden in the spleens or livers of infected mice nor affected serum TNF-\u03b1 levels.<\/jats:p>","DOI":"10.1128\/aac.42.9.2336","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T00:33:24Z","timestamp":1539045204000},"page":"2336-2341","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of Tumor Necrosis Factor Alpha Alters Resistance to<i>Mycobacterium avium<\/i>Complex Infection in Mice"],"prefix":"10.1128","volume":"42","author":[{"given":"Shukal","family":"Bala","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Division of Special Pathogen and Immunologic Drug Products (HFD-590)1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L.","family":"Hastings","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Division of Special Pathogen and Immunologic Drug Products (HFD-590)1 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazem","family":"Kazempour","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Division of Antiviral Drug Products (HFD-530),2 Food and Drug Administration, Rockville, Maryland 20857"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly","family":"Inglis","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Division of Antiviral Drug Products (HFD-530),2 Food and Drug Administration, Rockville, Maryland 20857"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walla L.","family":"Dempsey","sequence":"additional","affiliation":[{"name":"<!--label omitted: 2-->Division of Antiviral Drug Products (HFD-530),2 Food and Drug Administration, Rockville, Maryland 20857"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.9.3962-3971.1994"},{"key":"e_1_3_2_3_2","first-page":"131","article-title":"Immunological studies of NK cell deficient beige mice. II. Analysis of T-lymphocyte functions in beige mice.","volume":"66","author":"Baca M. E.","year":"1989","unstructured":"Baca M. E. Mowat A. M. Parott D. M. V. Immunological studies of NK cell deficient beige mice. II. Analysis of T-lymphocyte functions in beige mice. Immunology 66 1989 131 137","journal-title":"Immunology"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0008-8749(81)90382-8","article-title":"An analysis of the natural killer cell defect in beige mice.","volume":"61","author":"Beck B. N.","year":"1981","unstructured":"Beck B. N. Henney C. S. An analysis of the natural killer cell defect in beige mice. Cell. Immunol. 61 1981 343 352","journal-title":"Cell. Immunol."},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.4049\/jimmunol.140.9.3006","article-title":"Tumor necrosis factor, alone or in combination with IL-2, but not IFN-\u03b3, is associated with macrophage killing of Mycobacterium avium complex.","volume":"140","author":"Bermudez L. E. M.","year":"1988","unstructured":"Bermudez L. E. M. Young L. S. Tumor necrosis factor, alone or in combination with IL-2, but not IFN-\u03b3, is associated with macrophage killing of Mycobacterium avium complex. J. Immunol. 140 1988 3006 3013","journal-title":"J. Immunol."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(90)90144-G"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.4049\/jimmunol.143.9.2996","article-title":"Treatment of experimental disseminated Mycobacterium avium complex infection in mice with recombinant IL-2 and tumor necrosis factor.","volume":"143","author":"Bermudez L. E. M.","year":"1989","unstructured":"Bermudez L. E. M. Stevens P. Kolonoski P. Wu M. Young L. S. Treatment of experimental disseminated Mycobacterium avium complex infection in mice with recombinant IL-2 and tumor necrosis factor. J. Immunol. 143 1989 2996 3000","journal-title":"J. Immunol."},{"key":"e_1_3_2_8_2","first-page":"549","article-title":"Production of TNF-\u03b1, IL-6 and TGF-\u03b2, and expression of receptors for TNF-\u03b1 and IL-6, during Mycobacterium avium infection.","volume":"84","author":"Champsi J.","year":"1995","unstructured":"Champsi J. Young L. S. Bermudez L. E. Production of TNF-\u03b1, IL-6 and TGF-\u03b2, and expression of receptors for TNF-\u03b1 and IL-6, during Mycobacterium avium infection. Immunology 84 1995 549 554","journal-title":"Immunology"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1365-2249.1991.tb05662.x","article-title":"Modulation of Mycobacterium avium growth in vivo by cytokines: involvement of tumor necrosis factor in resistance to atypical mycobacteria.","volume":"83","author":"Denis M.","year":"1991","unstructured":"Denis M. Modulation of Mycobacterium avium growth in vivo by cytokines: involvement of tumor necrosis factor in resistance to atypical mycobacteria. Clin. Exp. Immunol. 83 1991 466 471","journal-title":"Clin. Exp. Immunol."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.15.5974"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.6.2100-2106.1997"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1182\/blood.V77.8.1653.1653","article-title":"Pentoxifylline (Trental) decreases the replication of the human immunodeficiency virus type 1 in human peripheral blood mononuclear cells and in cultured T cells.","volume":"77","author":"Fazely F.","year":"1991","unstructured":"Fazely F. Dezube B. J. Allen-Ryan J. Pardee A. B. Ruprecht R. M. Pentoxifylline (Trental) decreases the replication of the human immunodeficiency virus type 1 in human peripheral blood mononuclear cells and in cultured T cells. Blood 77 1991 1653 1656","journal-title":"Blood"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.34.9.1629"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V43.2.201.201"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.8.1647"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1164\/ajrccm\/139.5.1098","article-title":"Susceptibility of beige mice to Mycobacterium avium complex infections by different routes of challenge.","volume":"139","author":"Gangadharam P. R. J.","year":"1989","unstructured":"Gangadharam P. R. J. Perumal V. K. Parikh K. Podapati N. R. Taylor R. B. Farhi D. C. Iseman M. D. Susceptibility of beige mice to Mycobacterium avium complex infections by different routes of challenge. Am. Rev. Respir. Dis. 139 1989 1098 1104","journal-title":"Am. Rev. Respir. Dis."},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/jac\/39.2.189","article-title":"Enhancement of antibacterial activity of clofazimine against Mycobacterium avium-Mycobacterium intracellulare complex infection induced by IFN-\u03b3 is mediated by TNF-\u03b1.","volume":"39","author":"Gomez-Flores R.","year":"1997","unstructured":"Gomez-Flores R. Tucker S. D. Kansal R. Tamez-Guerra R. Mehta R. T. Enhancement of antibacterial activity of clofazimine against Mycobacterium avium-Mycobacterium intracellulare complex infection induced by IFN-\u03b3 is mediated by TNF-\u03b1. J. Antimicrob. Chemother. 39 1997 189 197","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/ana.410290106","article-title":"Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1 infected patients with central nervous system involvement.","volume":"29","author":"Grimaldi L. M. E.","year":"1991","unstructured":"Grimaldi L. M. E. Martino G. V. Franciotta D. M. Brustia R. Castagna A. Pristera R. Lazzarin A. Elevated alpha-tumor necrosis factor levels in spinal fluid from HIV-1 infected patients with central nervous system involvement. Ann. Neurol. 29 1991 21 25","journal-title":"Ann. Neurol."},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","unstructured":"Grosset J. H. 1994. Assessment of new therapies for infection due to the Mycobacterium avium complex: appropriate use of in vitro and in vivo testing. Clin. Infect. Dis. 3 (Suppl.):S233\u2013S236.","DOI":"10.1093\/clinids\/18.Supplement_3.S233"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.2.528-533.1995"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.6.1369"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(88)90576-1"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.13.5974"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/S0140-6736(89)92788-8","article-title":"Augmentation of in vitro HIV replication in peripheral blood mononuclear cells of AIDS and ARC patients by tumor necrosis factor.","author":"Mischihiko S.","year":"1989","unstructured":"Mischihiko S. Yamamoto N. Shinozaki F. Shimada K. Soma G. Kobayashi N. Augmentation of in vitro HIV replication in peripheral blood mononuclear cells of AIDS and ARC patients by tumor necrosis factor. Lancet i 1989 1206 1207","journal-title":"Lancet"},{"key":"e_1_3_2_25_2","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1084\/jem.177.6.1675","article-title":"Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation.","volume":"177","author":"Moreira A. L.","year":"1993","unstructured":"Moreira A. L. Sampaio E. P. Zmuidzinas A. Frindt P. Smith K. A. Kaplan G. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J. Exp. Med. 177 1993 1675 1680","journal-title":"J. Exp. Med."},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199605000-00004"},{"key":"e_1_3_2_27_2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1093\/infdis\/171.2.393","article-title":"Pharmacologic inhibitors of tumor necrosis factor production exert differential effects in lethal endotoxemia and in infection with live microorganisms in mice.","volume":"171","author":"Netea M. G.","year":"1995","unstructured":"Netea M. G. Blok W. L. Kullberg B.-J. Bemelmans M. Vogels T. E. Buurman W. A. van der Meer J. W. M. Pharmacologic inhibitors of tumor necrosis factor production exert differential effects in lethal endotoxemia and in infection with live microorganisms in mice. J. Infect. Dis. 171 1995 393 399","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.2.782"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1089\/jir.1997.17.69","article-title":"Treatment of an infected murine macrophage cell line (J774A.1) with interferon-\u03b3 but not tumor necrosis factor-\u03b1 or live Mycobacterium intracellulare alone modulates the expression of adhesion molecules.","volume":"17","author":"Pourshafie M. R.","year":"1997","unstructured":"Pourshafie M. R. Sonnenfeld G. Treatment of an infected murine macrophage cell line (J774A.1) with interferon-\u03b3 but not tumor necrosis factor-\u03b1 or live Mycobacterium intracellulare alone modulates the expression of adhesion molecules. J. Interferon Cytokine Res. 17 1997 69 75","journal-title":"J. Interferon Cytokine Res."},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/278451a0","article-title":"The beige mutation in the mouse selectively impairs natural killer cell function.","volume":"278","author":"Roder J.","year":"1979","unstructured":"Roder J. Duwe A. The beige mutation in the mouse selectively impairs natural killer cell function. Nature (London) 278 1979 451 453","journal-title":"Nature (London)"},{"key":"e_1_3_2_31_2","first-page":"2174","article-title":"The beige mutation in the mouse. II. Selectivity of the natural killer (NK) cell defect.","volume":"123","author":"Roder J. C.","year":"1979","unstructured":"Roder J. C. Lohmann-Matthes M. L. Domzig W. Wigzell H. The beige mutation in the mouse. II. Selectivity of the natural killer (NK) cell defect. J. Immunol. 123 1979 2174 2181","journal-title":"J. Immunol."},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/infdis\/172.3.863","article-title":"Pentoxifylline impairs macrophage defense against Mycobacterium avium complex.","volume":"172","author":"Sathe S. S.","year":"1995","unstructured":"Sathe S. S. Sarai A. Tsigler D. Kumar P. Pentoxifylline impairs macrophage defense against Mycobacterium avium complex. J. Infect. Dis. 172 1995 863 866","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_33_2","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1093\/infdis\/170.2.484","article-title":"Pentoxifylline aggravates impairment in tumor necrosis factor-\u03b1 secretion and increases mycobacterial load in macrophages from AIDS patients with disseminated Mycobacterium avium-intracellulare complex infection.","volume":"170","author":"Sathe S. S.","year":"1994","unstructured":"Sathe S. S. Sarai A. Tsigler D. Nedunchezian D. Pentoxifylline aggravates impairment in tumor necrosis factor-\u03b1 secretion and increases mycobacterial load in macrophages from AIDS patients with disseminated Mycobacterium avium-intracellulare complex infection. J. Infect. Dis. 170 1994 484 487","journal-title":"J. Infect. Dis."},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/295240a0","article-title":"Defective T-cell response in beige mutant mice.","volume":"295","author":"Saxena R. K.","year":"1982","unstructured":"Saxena R. K. Saxena Q. B. Adler W. H. Defective T-cell response in beige mutant mice. Nature (London) 295 1982 240 241","journal-title":"Nature (London)"},{"key":"e_1_3_2_35_2","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.4049\/jimmunol.146.9.3165","article-title":"Bidirectional effects of cytokines on the growth of Mycobacterium avium within human monocytes.","volume":"146","author":"Shiratsuchi H.","year":"1991","unstructured":"Shiratsuchi H. Johnson J. L. Ellner J. J. Bidirectional effects of cytokines on the growth of Mycobacterium avium within human monocytes. J. Immunol. 146 1991 3165 3170","journal-title":"J. Immunol."},{"key":"e_1_3_2_36_2","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.4049\/jimmunol.160.4.1789","article-title":"Pentoxifylline inhibits Ig \u03ba gene transcription and rearrangement in pre-B cells.","volume":"160","author":"Wang W.","year":"1998","unstructured":"Wang W. Rath S. Durdik J. M. Sen R. Pentoxifylline inhibits Ig \u03ba gene transcription and rearrangement in pre-B cells. J. Immunol. 160 1998 1789 1795","journal-title":"J. Immunol."},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1365-2249.1991.tb05688.x","article-title":"Induction of anti-mycobacterial and anti-listerial activity of human monocytes requires different activation signals.","volume":"85","author":"Zerlauth G.","year":"1991","unstructured":"Zerlauth G. Eibl M. M. Mannhalter J. W. Induction of anti-mycobacterial and anti-listerial activity of human monocytes requires different activation signals. Clin. Exp. Immunol. 85 1991 90 97","journal-title":"Clin. Exp. Immunol."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.42.9.2336","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.42.9.2336","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T19:48:34Z","timestamp":1693943314000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.42.9.2336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,9]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[1998,9]]}},"alternative-id":["10.1128\/AAC.42.9.2336"],"URL":"https:\/\/doi.org\/10.1128\/aac.42.9.2336","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,9]]},"assertion":[{"value":"1998-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-06-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}