Search

Polymorphonuclear (PMN) functions were assessed in 93 non-selected hospitalized patients, 32 active, healthy, elderly controls and 29 young controls. The results confirm the impairment of PMN functions in the aged. However, PMN functions in hospitalized older persons are similar to those in non-institutionalized controls, and underlying diseases and treatment do not seem to aggravate the PMN impairment. Thus, it can be assumed that the frequent and severe infections afflicting the hospitalized aged are due to the alteration of the other host-defense mechanisms.

It has been shown that isoprinosine, an antiviral drug, possesses immunoregulatory properties. To complement such studies, the effects of increasing concentrations of isoprinosine on several functions of polymorphonuclear leukocytes (PMN) [chemotaxis, adhesiveness, particle ingestion, quantitative reduction of nitroblue tetrazolium dye (NBT), candidacidal activity] were investigated. At higher concentrations (greater than 10/gmg/ml) this drug produced a dose-related depressive effect, more pronounced on chemotaxis than on NBT reduction. A significant decrease of adhesiveness was observed only with the highest concentration (1000 μg/ml) of isoprinosine; the other tests were not affected. Thus, these in vitro experiments could not demonstrate any stimulatory effect of isoprinosine on normal human PMN. However, these results do not exclude the possibility of a beneficial effect of the drug on functionally altered PMN.

To determine whether normal aging interferes with the functional capability of polymorphonuclear leukocytes (PMNs), 6 tests of PMN function were performed in 285 healthy subjects whose ages ranged from 20 to 97 years. A second selection based upon blood measurement and a review of medical histories 6 months later, eliminated 68 subjects. The 217 remaining persons were sub-classed by age into 7 groups including equal numbers of males and females. The functional properties of PMNs in the aged, when compared to those of younger adults, were characterized by: (a) a decrease in the chemotactic response in the 80+ age group: (b) increased adherence, with onset after age 70, maximal after age 80; (c) a progressive decrease of NBT dye reduction capability, up to age 70-79, followed by an unexplained increase of the mean value after age 80; (d) diminished Candida-killing activity, appearing in the 60+ group and becoming lowest in the oldest group; and (e) lack of changes in spontaneous migration and endocytosis. The mechanisms by which this impairment occurs are hypothetical. It is proposed that normal PMNs, after leaving the bone marrow, are influenced by various humoral components such as metabolic byproducts or immune processes altered by aging. Thus the defective PMN may represent only another victim of the aging process.

The slime of Pseudomonas aeruginosa markedly impaired the in vitro motility, endocytosis, and phagosome formation of normal human polymorphonuclear neutrophils. This profound impairment of neutrophils, although without alteration of their viability, may contribute to the virulence of this microorganism.

The function of polymorphonuclear leukocytes (PMNs) has previously been shown to be impaired in smokers in comparison with healthy nonsmokers. Potent inhibition of PMN chemotaxis has been achieved with whole tobacco smoke, the gas phase of smoke, and a water-soluble extract of whole smoke. In the present work several aspects of PMN function were studied after exposure to water-soluble fraction of the particle phase of tobacco smoke collected on glass fiber filters. These tests included capillary tube random migration, chemotaxis under agarose, phagocytosis of yeasts, Nitro Blue Tetrazolium dye reduction, and whole-blood bactericidal activity. The water extract of the particle fraction of smoke had a high content of nicotine when compared with the levels achieved in plasma of smokers and a much lower concentration of aldehydes when compared with the gas phase of smoke. It had no cytotoxic effect and did not affect phagocytosis, oxygen consumption, or bactericidal activity. Nitro Blue Tetrazolium reduction of both resting and stimulated PMNs was significantly decreased only with the most concentrated solution. The tested solutions exerted a dose-related depressive effect on capillary tube random migration, whereas the random migration measured in the agarose chemotaxis test was normal. Nevertheless, the chemotactic response to a caseine solution was significantly decreased. The same tests were performed in the presence of several concentrations of a nicotine solution and the only test to be affected was the capillary tube random migration, and, that only at a very high concentration. The results of this study contribute to the more precise delineation of the extent of the dysfunction of PMNs exposed to tobacco smoke components and indicate that deleterious products are released from the particle phase of the smoke, which deposits all along the respiratory tree.