Search PubMed⌕ Search

Biomedical subjects

Jan A Moynihan

Publications and source records attributed to Jan A Moynihan.

10 recordsLinked to original sources
PubMed2005

Modulation of the innate immune response to HSV-1 following acute administration of morphine: role of hypothalamo-pituitary-adrenal axis.

A single injection of morphine significantly increased interferon (IFN)-beta and IFN-alpha mRNA in spleens from herpes simplex virus (HSV)-1 infected male Balb/cByJ mice. However, significant suppression of IFN-gamma and interleukin (IL)-12 production was observed in spleens from morphine-treated mice. Pretreatment with RU486 blocked morphine-induced increases in IFN-beta, and reversed the suppression of IFN-gamma. However, RU486 did not restore IFN-alpha or IL-12. The results suggest that a single exposure to morphine 4 h prior to infection can significantly alter innate immune responses to a viral pathogen, and that these effects are partially mediated by glucocorticoids.

Analysis of Variance↗
PubMed2004

Age effects on macrophage function vary by tissue site, nature of stimulant, and exercise behavior.

We explored the effects of aging on macrophage function in male BALB/c mice from three age groups: young (2 months), middle-aged (12 months), and old (21 months). Macrophages were collected from alveoli, peritonea, and spleens of each age group. Cells were cultured in vitro with LPS or LPS+IFN-gamma and assayed for production of IL-1, IL-12, NO, and TNF-alpha. Using herpes simplex virus-1, age-related changes in intrinsic antiviral resistance (plaque assay) and extrinsic antiviral resistance (NO and TNF-alpha production) were determined in alveolar and/or peritoneal macrophages. Effects of chronic exercise on age-related macrophage changes were examined. In vitro, macrophages from the alveoli and spleen of older mice generally produced more cytokine and NO compared to younger counterparts. Conversely, macrophages from the peritonea of older mice generally produced less cytokine and NO in vitro compared to younger counterparts. Alveolar macrophages from both old and young mice showed higher intrinsic antiviral resistance to HSV-1 compared to middle-aged mice, while peritoneal macrophages from young mice showed reduced intrinsic resistance compared to those from both middle-aged and old mice. When challenged with HSV-1, a trend towards decreased peritoneal macrophage production of TNF-alpha and decreased alveolar macrophage production of IL-12 with advancing age was found. Chronic moderate exercise tended to reverse age-associated changes in macrophage function in old mice.

Aging↗
PubMed2004

Stress causes a further decrease in immunity to herpes simplex virus-1 in immunocompromised hosts.

Physical or psychological stress can modulate immune responses in normal subjects. The effects of stress on immunity in immunocompromised hosts, however, have not been extensively investigated. Here we assess relationships among footshock stress (FS), infection with herpes simplex virus-1 (HSV-1), and immunosuppression by cyclophosphamide (CY) during the active immune response to virus in BALB/c mice. Without FS, CY significantly decreased survival and body weight gain, splenic leukocyte numbers, in vivo serum cytokine level and in vitro splenocyte cytokine production during HSV-1 infection. FS alone also significantly inhibited cell mediated anti-viral responses to HSV-1. However, FS in combination with certain CY doses led to a further significant decrease in host responses compared to either CY or FS treatment alone, including decreased survival rate, increased weight loss, lowered leukocyte numbers, reduced cytokine production in vivo and in vitro, and decreased numbers of cytokine-producing cells (IL-12 and IFNgamma). In contrast, CY, but not FS, significantly reduced in vivo anti-HSV-1 antibody secretion. These data support the hypothesis that stress can further reduce host immune responses in immunocompromised individuals. Thus, stress levels of patients should be taken into consideration prior to clinical treatment with immunosuppressants.

Animals↗
PubMed2003

Mechanisms of stress-induced modulation of immunity.

The purpose of this chapter is to discuss the wealth of animal studies of stress-induced modulation of immunity, and to relate our understanding of stress and immunity to clinical populations, particularly cancer patients.

Animals↗
PubMed2003

Sympathetic nerve destruction in spleen in murine AIDS.

In susceptible strains of mice, the LP-BM5 mixture of murine retroviruses induces the fatal immunodeficiency disease known as murine acquired immunodeficiency syndrome (murine AIDS or MAIDS). We have previously reported that murine AIDS produces a profound depletion of splenic norepinephrine (NE). Here, we demonstrate that NE depletion is limited to the spleen, a major site affected by LP-BM5 infection. NE depletion in the spleen is first observed at two weeks following LP-BM5 inoculation, concurrent with the onset of splenomegaly, and continues through 12 weeks post-infection. Neuroanatomical studies revealed that the reduction in NE is due to destruction of splenic sympathetic nerve fibers. Administration of the NE reuptake blocker desipramine did not prevent LP-BM5-induced NE depletion, suggesting that destruction is not caused by excess release and reuptake of NE. Elucidating the mechanism of MAIDS-induced sympathetic nerve destruction may provide insight into autonomic and peripheral neuropathies reported in people with AIDS.

Adrenergic Uptake Inhibitors↗
PubMed2002

The effects of chemical sympathectomy on T-cell cytokine responses are not mediated by altered peritoneal exudate cell function or an inflammatory response.

Ablation of the sympathetic nervous system by chemical sympathectomy is a standard model for the study of sympathetic nervous system regulation of immune function. We have previously documented that chemical denervation results in enhanced antigen-specific, but suppressed mitogen-induced, cytokine production by spleen cells. In our investigation into the mechanisms of sympathectomy-induced immune alterations, we first evaluated the peritoneal environment into which the protein antigen keyhole limpet hemocyanin is administered. Denervation resulted in increased production of tumor necrosis factor-alpha by peritoneal exudate cells and these cells appeared to have enhanced antigen presenting capability. We hypothesized that nerve terminal destruction may be inducing an inflammatory response by monocyte/macrophages and other cell types throughout the periphery that could differentially alter subsequent mitogen versus antigen-specific responses. However, no evidence of sympathectomy-induced systemic or local splenic inflammatory responses was observed, as indicated by measuring the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta. These experiments indicate that an inflammatory response is not likely to be responsible for sympathectomy-induced immune alterations, eliminating a potential confounding factor in interpreting sympathectomy studies.

Animals↗
PubMed2002

Chemical sympathectomy has no effect on the severity of murine AIDS: murine AIDS alone depletes norepinephrine levels in infected spleen.

Numerous studies have shown that alterations in sympathetic nervous system (SNS) function produced by beta-adrenergic receptor blockade or chemical sympathectomy can produce changes in T and B lymphocyte function and both innate and acquired immune responses. However, fewer studies have investigated changes in immune response following SNS alterations in animal models of disease. We tested whether blocking SNS activity using 6-OHDA or the beta-receptor antagonist nadolol alters the typical pattern in production of T helper 1 (Th1) and Th2 cytokines seen in cultures of spleen cells from C57BL/6 mice infected with murine AIDS (MAIDS). We found that neither method of sympathetic blockade affected cytokine response to MAIDS. We also found that the norepinephrine concentration and content of the spleen were reduced dramatically by the MAIDS infection itself at 3 and 6 weeks after LP-BM5 inoculation. This finding has not been previously reported in mice with MAIDS and suggests that the viral infection itself produces a functional sympathectomy in the spleen, a target of that infection.

Adrenergic beta-Antagonists↗
PubMed2002

Contrasting pattern of cytokines in antigen- versus mitogen-stimulated splenocyte cultures from chemically denervated mice.

Sympathetic nervous system (SNS) regulation of immune function has been studied by ablating the SNS with a peripheral injection of the neurotoxin 6-hydroxydopamine (6-OHDA). Our previous data indicate that sympathectomy of mice results in enhanced antibody production and in vitro levels of antigen-specific IL-2 and IFN-gamma. Other investigators have observed either increased or decreased immune function following sympathectomy. Here we present data showing that culture supernatants from spleen cells from the same denervated animals contain increased IL-2 and IFN-gamma levels in response to antigen-specific (keyhole limpet hemocyanin (KLH)) stimulation, but decreased cytokines levels in response to the T cell mitogen Con A compared to vehicle control mice. KLH-induced type 2 cytokines were also increased; no decrease in Con A-stimulated type 2 cytokines was observed. We evaluated whether the antigen presenting cell (APC) or the T cell might be the main target of the observed sympathectomy effects. Cell separation and mixing experiments suggest that the sympathectomy-induced alterations of antigen-specific and mitogen-induced type 1 cytokines are mediated primarily via the T cell. These data directly address some apparent discrepancies in the literature, and highlight potential regulatory sites to be further investigated in pathways of neural-immune communication.

Animals↗
PubMedDate not supplied

Psychosocial factors and the response to influenza vaccination in older adults.

OBJECTIVE: We examined the influence of psychological state (depression, negative affect, perceived stress) and social support on pre- and post-vaccination response to influenza vaccine. METHODS: Venous blood was drawn from 37 nursing home residents before and following injection of the trivalent influenza vaccine (comprised of the New Caledonia (NC), Hong Kong (HK), and Panama (Pan) strains of flu). The Geriatric Depression Scale, Perceived Stress Scale, Positive and Negative Affect Schedule, and Multidimensional Scale of Perceived Social Support were completed following the initial blood draw. RESULTS: Social support and perceived stress were correlated with pre-vaccine antibody responses to two of the three vaccine components (HK and NC). Social support was negatively correlated with both pre- and post-vaccine titers to Pan. Depression, positive affect, and negative affect were not related to vaccine response. CONCLUSIONS: Perceived stress and social support influence the rate of decline of antibody titers to previous exposures to some strains of influenza occurring either naturally or via deliberate vaccination.

Affect↗