Treatment with AM3 restores defective T-cell function in COPD patients.
BACKGROUND
Lymphocyte alterations have been associated with an increased prevalence of acute respiratory infections in COPD patients. AM3 is an oral immunomodulator that normalizes the defective functions of peripheral blood natural killer and phagocytic cells in COPD patients and improves their health-related quality of life.


OBJECTIVE
To characterize putative systemic abnormalities of the T-cell compartment in COPD patients, and to investigate whether AM3 can restore such abnormalities.


METHODS
The study was a randomized, prospective, double-blind, placebo-controlled trial in a cohort of COPD patients. The results were also compared to those of nonsmoker and ex-smoker healthy control subjects.


METHODS
Outpatient departments of four hospitals.


METHODS
Seventy COPD patients were randomized to receive either AM3 or a placebo orally for 90 consecutive days. Populations of 36 healthy nonsmokers and 36 healthy ex-smokers were used as control subjects.


METHODS
Peripheral blood mononuclear cell (PBMC) proliferation and production of interleukin (IL)-2, IL-4, IL-12p40, tumor necrosis factor-alpha, and interferon (IFN)-gamma proteins in response to the T-cell polyclonal mitogens were assessed at baseline and at the end of treatment.


RESULTS
The proliferative response was significantly decreased in COPD patients. Decreased production of IFN-gamma was the only defect in the profiles of the cytokine measures, and was selectively observed in COPD patients, but not in nonsmoker and ex-smoker healthy control subjects. Treatment with AM3 significantly restored the PBMC proliferative response to polyclonal mitogens and significantly promoted stimulated IFN-gamma production in these patients. The normalization of these proliferative responses was not related to significant variations in the numbers of peripheral blood monocytes, CD3+, CD4+, CD8+ cells or of any major naïve/memory/activated T-cell subset. The increased IFN-gamma production in the AM3 study arm was associated with an increase in the mean of number of IFN-gamma molecules produced per CD8+ T cells.


CONCLUSIONS
PBMCs of COPD patients showed clear functional T-lymphocyte abnormalities that are rescued by AM3 treatment.
Reyes
Eduardo
E
Departamento de Medicina, Universidad de Alcalá, Carretera Madrid-Barcelona, Km 33,600, E-28871 Alcalá de Henares, Madrid, Spain. eduardo.reyes@uah.es
Prieto
Alfredo
A
de la Hera
Antonio
A
de Lucas
Pilar
P
Alvarez-Sala
Rudolfo
R
Alvarez-Sala
José Luis
JL
Alvarez-Mon
Melchor
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000368:Aged; D002130:Calcium Phosphates / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006020:Glycopeptides / Q000627:therapeutic use*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology*; D011788:Quality of Life; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000276:Adjuvants, Immunologic; D002130:Calcium Phosphates; D006020:Glycopeptides; D007371:Interferon-gamma; C038773:Immunoferon