Abstract | BACKGROUND: METHODS: Consenting adults with symptomatic sarcoidosis (n 5 13) were randomly assigned to receive 12 weeks of nicotine treatment plus conventional therapy or conventional therapy alone. Obtained blood cells were evaluated for their responsiveness to selected Toll-like receptor (TLR) and nucleotide oligomerization domain-like receptor ligands and T cell surface marker expression before and after nicotine treatment. Asymptomatic patients (n 5 6) and disease-free subjects (n 5 6) served as comparative control subjects. Adverse events were monitored for the duration of the study. RESULTS: Compared with the asymptomatic group, symptomatic patients had impaired peripheral responses to TLR2, TLR4, and TLR9 ligands (anergy) and reduced peripheral populations of CD4 1 FoxP3 1 regulatory T cells (Tregs). Nicotine treatment was associated with restoration of TLR2 and TLR9 responsiveness, and expansion of Tregs, including the CD4 1 CD25 2 FoxP3 1 phenotype. There were no serious adverse events or signs of nicotine dependency. CONCLUSIONS:
Nicotine treatment in active pulmonary sarcoidosis was well tolerated and restored peripheral immune responsiveness to TLR2 and TLR9 agonists and expansion of FoxP3 1 Tregs, including a specific “preactivated” (CD25 2 ) phenotype. The immune phenotype of patients with symptomatic sarcoidosis treated with nicotine closely resembled that of asymptomatic patients, supporting the notion that nicotine treatment may be beneficial in this patient population.
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Authors | Mark W Julian, Guohong Shao, Larry S Schlesinger, Qin Huang, David G Cosmar, Nitin Y Bhatt, Daniel A Culver, Robert P Baughman, Karen L Wood, Elliott D Crouser |
Journal | Chest
(Chest)
Vol. 143
Issue 2
Pg. 461-470
(Feb 01 2013)
ISSN: 1931-3543 [Electronic] United States |
PMID | 22878868
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antigens, Surface
- FOXP3 protein, human
- Forkhead Transcription Factors
- Nicotinic Agonists
- TLR2 protein, human
- TLR9 protein, human
- Toll-Like Receptor 2
- Toll-Like Receptor 9
- Nicotine
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Topics |
- Antigens, Surface
(metabolism)
- Female
- Forkhead Transcription Factors
(metabolism)
- Humans
- Immunity, Cellular
(drug effects)
- Male
- Middle Aged
- Nicotine
(pharmacology, therapeutic use)
- Nicotinic Agonists
(pharmacology, therapeutic use)
- Phenotype
- Sarcoidosis, Pulmonary
(drug therapy, metabolism, pathology)
- T-Lymphocytes, Regulatory
(metabolism, pathology)
- Toll-Like Receptor 2
(immunology, metabolism)
- Toll-Like Receptor 9
(immunology, metabolism)
- Treatment Outcome
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