Abstract
Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in immune response changes, alterations in immunological phenotypes, and ultimately increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV-1 disease, particularly in aging individuals, the HIV-1 transgenic (HIV-1Tg) rat model was utilized. HIV-1Tg rats were challenged with lipopolysaccharide (LPS) to determine immunological alterations during the aging process. LPS is known to cause an imbalance in cytokine and chemokine release, and provides a method to identify changes in immune responses to bacterial infection in an HIV animal model. An immune profile and accompanying cellular consequences as well as changes in inflammatory cytokine and chemokine release related to age and genotype were assessed in HIV-1Tg rats. The percentage of T cells decreased with age, particularly T cytotoxic cells, whereas T helper cells increased with age. Neutrophils and monocytes increased in HIV-1Tg rats during maturation compared to age-matched F344 control rats. Aging HIV-1Tg rats displayed a significant increase in the pro-inflammatory cytokines, IL-6 and TNF-α, along with an increase in the chemokine, KC/GRO, in comparison to age-matched controls. Our data indicate that immunophenotype and immune responses can change during aging in HIV-positive individuals. This information could be important in determining the most beneficial age-dependent therapeutic treatment for HIV patients.
Highlights
Life expectancy of people infected with the human immunodeficiency virus (HIV) is increasing and approximates that of the general population
Mature HIV-1 transgenic (HIV-1Tg) rats have decreased CD4+ and CD8+ effector and memory cells and an increased number of naıve cells [17,18]. These findings suggest that aging may influence immune function of T cell populations in the HIV-1Tg rat
CD3+ T cell lymphocytes (Fig. 2A) were significantly increased in 2 mo old HIV-1Tg rats compared to age-matched F344 animals
Summary
Life expectancy of people infected with the human immunodeficiency virus (HIV) is increasing and approximates that of the general population. The current median life expectancy for an HIV patient receiving effective therapy exceeds 70 yrs of age [1]. A recent publication from the United Kingdom reported that the percentage of HIV-positive individuals who are over 50 yrs of age has risen from 12% in 2002 to 22% in 2011 due to an increase in the length of survival and a surge in the incidence of newly identified older HIV patients [5]. As the population of HIV-positive patients ages, they often develop other ailments, including cardiovascular disease, cancer, osteoporosis, and liver and renal disease, as well as the neurocognitive deficiencies more commonly associated with aging and chronic inflammation than with HIV infection [6,7,8,9,10,11,12]
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