TY - JOUR
T1 - Neutralization of Tumor Necrosis Factor (TNF) by antibody but not TNF receptor fusion molecule exacerbates chronic murine tuberculosis
AU - Plessner, Hillarie L.
AU - Lin, P. Ling
AU - Konno, Tadahiko
AU - Louie, James S.
AU - Kirschner, Denise
AU - Chan, John
AU - Flynn, Jo Anne L.
N1 - Funding Information:
Financial support: National Institutes of Health (grants RO1 HL71241 and HL68526); Ellison Medical Foundation; Amgen, Inc. (research grant). Murine tumor necrosis factor receptor 2–Fc was provided by Amgen, Inc.
PY - 2007/6/1
Y1 - 2007/6/1
N2 - Tumor necrosis factor (TNF) plays an essential role in the immunologic maintenance of Mycobacterium tuberculosis infection. Although an increased rate of tuberculosis has been reported in humans treated with anti-TNF biological agents, disparate rates of disease have been observed between those treated with infliximab, an anti-TNF antibody, and etanercept, a TNF-neutralizing TNF receptor (TNFR) fusion molecule. We compared the effects of anti-TNF antibody and soluble TNFR fusion molecule in the murine model of tuberculosis. Systemic TNF neutralization was equivalent between these molecules, and both resulted in rapid morbidity at the initiation of infection. During chronic infection, administration of the receptor fusion molecule allowed the control of infection, whereas antibody treatment caused mice to die within a month. We provide evidence of decreased penetration into the granulomas by the receptor fusion molecule, compared with antibody. These findings begin to clarify the mechanistic difference between anti-TNF agents and their role in the exacerbation of tuberculosis.
AB - Tumor necrosis factor (TNF) plays an essential role in the immunologic maintenance of Mycobacterium tuberculosis infection. Although an increased rate of tuberculosis has been reported in humans treated with anti-TNF biological agents, disparate rates of disease have been observed between those treated with infliximab, an anti-TNF antibody, and etanercept, a TNF-neutralizing TNF receptor (TNFR) fusion molecule. We compared the effects of anti-TNF antibody and soluble TNFR fusion molecule in the murine model of tuberculosis. Systemic TNF neutralization was equivalent between these molecules, and both resulted in rapid morbidity at the initiation of infection. During chronic infection, administration of the receptor fusion molecule allowed the control of infection, whereas antibody treatment caused mice to die within a month. We provide evidence of decreased penetration into the granulomas by the receptor fusion molecule, compared with antibody. These findings begin to clarify the mechanistic difference between anti-TNF agents and their role in the exacerbation of tuberculosis.
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U2 - 10.1086/517519
DO - 10.1086/517519
M3 - Article
C2 - 17471434
AN - SCOPUS:34249007153
SN - 0022-1899
VL - 195
SP - 1643
EP - 1650
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -