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. Objectives To characterize putative systemic abnormalities of the T-cell compartment in COPD patients, and to investigate whether AM3 can restore such abnormalities. Design 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. Setting Outpatient departments of four hospitals. Patients 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. Measurements Peripheral blood mononuclear cell (PBMC) proliferation and production of interleukin (IL)-2, IL-4, IL-12p40, tumor necrosis factor-α, and interferon (IFN)-γ 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-γ 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-γ 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 naive/memory/activated T-cell subset. The increased IFN-γ production in the AM3 study arm was associated with an increase in the mean of number of IFN-γ molecules produced per CD8+ T cells. Conclusions PBMCs of COPD patients showed clear functional T-lymphocyte abnormalities that are rescued by AM3 treatment.