Depression of T Helper‐1 and Tuberculin Responses in Older Bed‐bound Patients

To the Editor: Older people are susceptible to infections from various pathogenic organisms. The risk of nosocomial infections is 3 to 5 times higher among older patients than among younger adults,1 and an increased risk of pneumonia mortality is found with limitations in activities of daily living (ADL) among older adults. It has been suggested that functional disability increases the risk of pneumonia-related mortality through malnutrition and subsequent decreased host defenses.2 However, it is unknown whether this heightened susceptibility to infection is a reflection of the disability-associated decline in the competence of the immune system. Therefore, we examined T helper-1 (Th1) responses and delayed-type hypersensitivity responses to tuberculin, implicated in several immune responses related to infection,3 in older patients confined to bed and compared the results with responses in age-matched healthy controls. Twenty-one patients, 13 women and eight men, mean age 80 years (SE ± 1), and 21 controls, 11 women and 10 men, mean age 79 years (SE ± 1), were assessed as total disability/dependence and full function/independence using the ADL index.4 The cause of disability was cerebral infarction and femoral-neck bone fracture. Tuberculin purified protein derivative (0.1 mL; 2 Tuberculin units; BCG Company Ltd., Tokyo, Japan) was injected intradermally on the dorsal side of the right forearm. After 48 hours, the diameter of induration was measured. To count the number of CD4 lymphocytes, whole blood labeled with a peridinin chlorphyll protein-conjugated monoclonal anti-CD4 antibody was analyzed with a FACSCalibur flow cytometer. To assess Th1 and Th2 subsets of CD4 lymphocytes, cells positive for anti-interferon-γ antibody labeled with fluoresceim isothiocyanate and those for anti-interleukin-4 antibody labeled with phycoerthrin under stimulation with 25 ng/mL phorbol 12-myristate 13 acetate, 1 μg/mL ionomycin, and 10 μg/mL brefeldin A were analyzed with a FASTIM-MUNE™ Cytokine System. This system measured the expression of cytokines inside the cells. Delayed-type hypersensitivity responses to tuberculin upon skin testing was significantly smaller in patients than in controls (5.7 [1.4] mm vs 14.0 [2.0] mm; P < .002). Likewise, negative tuberculin responses (<10 mm) were recorded in 81% of patients and 24% of controls (P < .01). The number of CD4 lympocytes differed significantly between patients and controls (672 [66] × 106/L vs 954 [91] × 106/L; P < .02). Likewise, the number of Th1 cells was significantly lower in patients than in controls (138 [14] × 106/L vs 243 [42] × 106/L; P < .01). However, Th2 cells were similar between patients and controls (19 [3] × 106/L vs 25 [3] × 106/L; P > .20). Th1 cells produce interferon-7 and tumor necrosis factor-β, which activate macrophages and are involved in delayed-type hypersensitivity reactions.3 The depression of delayed-type hypersensitivity responses to ubiquitous antigens with advancing age has been reported to correlate with mortality in old people. The delayed-type hypersensitivity responses to tuberculin, presumed to be dependent on Th1 cells, were clearly diminished in our older patients with functional disability, and this supplements a previous report of impaired responsiveness of human lymphocytes to phyto-hemagglutinin with ageing.5 The impaired, cell-mediated immunity may predispose to more numerous and more frequently fatal infections, especially illnesses associated with seasonal epidemics caused by new types or strains of bacterial or viral pathogens. The increased mortality associated with disability, therefore, could be explained in part by impaired cell-mediated immune functions in older patients.