Bradley S. Bender

Hematologic abnormalities in the acquired immune deficiency syndrome

Blood and marrow specimens were evaluated from 12 patients with the acquired immune deficiency syndrome (AIDS). Ten patients were anemic, eight leukopenic, and three thrombocytopenic. Pancytopenia was present in two patients and subsequently developed in two others. Reticulocyte counts were not increased in the anemic patients. The most common peripheral blood abnormalities were a left shift in the granulocyte series, lymphopenia, atypical lymphocytes, and vacuolated monocytes. Marrow cellularity was increased in five patients and reduced in three. Marrow reticulin was increased in 10 patients; in three of these, marrow could not be obtained by aspiration. Plasma cells were increased in number in every marrow aspirate, and there was a left shift in the myeloid series in most. Aggregates of atypical lymphocytes or a diffuse increase in marrow lymphocytes occurred in seven patients. An increase in histiocytes was observed in seven marrow aspirates; in five of these, the histiocytes were phagocytizing red cells, white cells, and platelets. Necrosis was present in four marrow specimens. These hematologic abnormalities reflect, in part, the presence of systemic infection, inflammation, and the inanition associated with them. However, the high incidence of myelofibrosis, alterations in marrow cellularity, pancytopenia, and hematophagic histiocytosis indicates that the bone marrow is a target organ in AIDS.

Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus

Compared with young mice, old mice infected with influenza virus have significantly higher pulmonary viral titres, although these can be reduced significantly with dietary vitamin E supplementation. T helper 1 (Th1) cytokines, especially interferon‐γ (IFN‐γ), play an important role in defending against influenza infection. However, there is an age‐associated loss of Th1 cytokine production. Prostaglandin E2 (PGE2) production, which increases with age, can modulate the T helper cell function by suppressing Th1 cytokine production. To investigate the mechanism of vitamin E supplementation on reduction of influenza severity in old mice, we studied the cytokine production by splenocytes, and PGE2 production by macrophages (Mφ), in young and old C57BL mice fed semipurified diets containing 30 (control) or 500 parts per million (ppm) (supplemented) vitamin E for 8 weeks, and then infected with influenza A/PC/1/73 (H3N2). Old mice fed the control diet had significantly higher viral titres than young mice; old mice fed the vitamin E‐supplemented diet had significantly lower pulmonary viral titres than those fed the control diet (P = 0·02 and 0·001 for overall age and diet effect, respectively). Following influenza infection, interleukin (IL)‐2 and IFN‐γ production was significantly lower in old mice than in young mice. Vitamin E supplementation increased production of IL‐2 and IFN‐γ in old mice; higher IFN‐γ production was associated with lower pulmonary viral titre. Old mice fed the control diet showed significantly higher lipopolysaccharide (LPS)‐stimulated Mφ PGE2 production than old mice fed the vitamin E diet or young mice fed either diet. There was no significant age difference in IL‐6, IL‐1β, or tumour necrosis factor‐α (TNF‐α) production by splenocytes. Young mice fed the vitamin E‐supplemented diet had significantly lower IL‐1β (day 7) and TNF‐α production (day 5) compared with those fed the control diet. Old mice fed the vitamin E‐supplemented diet had significantly lower TNF‐α production (day 2) than those fed the control diet. Our results indicate that the vitamin E‐induced decrease in influenza viral titre is mediated through enhancement of Th1 cytokines, which may be the result of reduced PGE2 production caused by vitamin E.

Vitamin E supplementation decreases lung virus titers in mice infected with influenza

Effects of vitamin E (E) supplementation on influenza infection were examined in young and old C57BL/6NIA mice fed 30 or 500 ppm of E for 6 weeks and subsequently infected with influenza A/Port Chalmers/1/73 (H3N2). Old mice fed 30 ppm of E had significantly higher lung virus titers on days 2 and 7 after infection than young mice fed 30 ppm of E. Titers on all 3 days were significantly lower in old mice fed 500 ppm of E than in those fed 30 ppm. Significant effects of E on lung virus titers in young mice were observed on only day 5, but E caused more reduction of virus titers in old than in young mice (25-fold vs. 15-fold). An age-associated decline in NK cell activity was restored by 500 ppm of E in old but not young mice. Pulmonary cytotoxic T lymphocyte activity on day 7 was not affected by age or E. These experiments demonstrate that high doses of E significantly enhance influenza viral clearance in aged mice but only modestly affect young mice.

Respirator tolerance in health care workers.

past 5 years, the following authors have received financial support and maintained affiliations as follows: Dr Lu-Yao has received clinical research funding from the New Jersey Commission on Cancer Research and the Agency for Healthcare Research and Quality and employment with HealthStat; Dr Peter Albertson has received clinical research funding from Sanofi-Aventis and consultation fees from Blue Cross/Blue Shield; and Dr Weichung Shih has received clinical research funding from Myriad. None of these entities contributed funding or played any role whatsoever in the design, interpretation, or drafting of our study or manuscript. We regret any misunderstanding that resulted from the omission of these disclosures.

Nutritional Formula Enhanced Immune Function and Reduced Days of Symptoms of Upper Respiratory Tract Infection in Seniors

Objectives: To assess whether an experimental nutritional formula, given as a supplement, would reduce days of symptoms of upper respiratory tract infection (URTI) and affect antibody and lymphocyte proliferative responses to influenza vaccine.

Nutritional formula improved immune profiles of seniors living in nursing homes

OBJECTIVES: To assess whether an experimental nutritional formula (EXP) supports immune function in seniors living in long‐term care facilities.

Infectious disease risk in the elderly.

Older persons suffer excessively from infectious diseases such as pneumonia and urinary tract infections. This article discusses some of the reasons for this additional morbidity and mortality, including the anatomical and physiological changes with aging, impairment of immune function, presence of co-morbid diseases, and delays in diagnosis and initiation of therapy.

UNIT 19.11 Influenza Virus

This unit contains several methods for infecting mice with influenza virus. It also includes protocols needed to propagate influenza virus in hen eggs, quantitate virus titers (in tissue culture medium and in influenza‐infected mouse serum), and adopt human isolates of influenza for growth in mice. Methods for measuring the 50% mouse lethal dose are also included. Finally, protocols for generating anti‐influenza cytotoxic T lymphocytes (CTL) from splenocyte precursors and harvesting pulmonary CTL following respiratory tract challenge of mice with influenza virus are provided.

Influenza immunization: intranasal live vaccinia recombinant contrasted with parenteral inactivated vaccine

To compare the efficacy and duration of the immune response to local and systemic vaccination, Balb/c mice were vaccinated either intraperitoneally (i.p.) with an inactivated A/PR/8/34 (H1N1) vaccine or intranasally (i.n.) with a vaccinia recombinant containing the H1 gene of influenza. The i.p. inactivated vaccine stimulated high serum IgG anti-influenza titres and protected the lungs against viral challenge for the duration of the experiment (17 months). Little nasal wash IgA was induced and the noses were susceptible to challenge. Animals vaccinated i.n. with the recombinant had lower serum IgG titres and the lungs showed poor protection against challenge. Nasal wash IgA titres were higher, however, and the noses were largely protected from viral challenge for 17 months.

Immunogenicity and efficacy of DNA vaccines encoding influenza A proteins in aged mice

Influenza is a leading cause of morbidity and mortality in older persons. The current influenza vaccine is only modestly successful, in part because of an age-related decline in immunogenicity and also because it induces only type-specified immunity. To overcome this, we evaluated DNA vaccines encoding A/PR8/34 haemagglutinin (HA) and nucleoprotein (NP) in young and aged BALB/c mice. Control mice were given formalin-inactivated A/PR8/34, control DNA, or a non-lethal dose of PR8. Aged mice given HA DNA developed slightly lower anti-HA serum antibodies than young mice; however, both young and aged mice were protected from a homotypic PR8 challenge. Following vaccination with NP DNA, both young and aged mice developed anti-NP bulk cytotoxic T-lymphocyte (CTL) activity and pCTL frequency similar to control animals. When challenged with a low dose of A/HK/68 (H3N2) influenza virus, both young mice and aged mice showed significant protection as measured by inhibition of weight loss. When challenged with a relatively high dose of A/HR/68 (H3N2) influenza virus, however, the anti-NP vaccine only partially protected young mice and failed to protect aged mice. These data demonstrate that DNA-based vaccines are immunogenic in aged animals, but suggest that factors other than the age-related decline in CTL activity also contribute to the increased morbidity and mortality of influenza in the elderly.